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PRESERVE: Study Comparing Etanercept in Combination With Methotrexate in Subjects With Rheumatoid Arthritis

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00565409
Collaborator
(none)
834
Enrollment
80
Locations
3
Arms
38
Duration (Months)
10.4
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To compare the efficacy of the combination of etanercept 50 mg once weekly plus methotrexate with that of methotrexate monotherapy in the treatment of rheumatoid arthritis over 88 weeks.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
834 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind Study Comparing the Safety & Efficacy of Once-Weekly Etanercept 50 mg, Etanercept 25 mg, & Placebo in Combination With Methotrexate in Subjects With Active Rheumatoid Arthritis
Study Start Date :
Mar 1, 2008
Actual Primary Completion Date :
May 1, 2011
Actual Study Completion Date :
May 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 1

Drug: Etanercept
Subcutaneous (SC), 50 mg, once weekly for 88 weeks
Other Names:
  • Enbrel

    • Drug: Methotrexate
    Oral, 15 to 25 mg (varying based on dosage the subject is receiving at the time of screening and may be increased at the discretion of the investigator through Week 28 to a maximum of 25 mg/week), once weekly for 88 weeks. If a subject experiences an adverse event (AE) during the study, Methotrexate may be decreased by 2.5 or 5.0 mg weekly (the minimum dose to stay in the study is 10 mg/week).
    Active Comparator: 2

    Drug: Etanercept
    Subcutaneous (SC), 25 mg, once weekly from week 36 to week 88.

    Drug: Methotrexate
    Oral, 15 to 25 mg (varying based on dosage the subject is receiving at the time of screening and may be increased at the discretion of the investigator through Week 28 to a maximum of 25 mg/week), once weekly for 88 weeks. If a subject experiences an adverse event (AE) during the study, Methotrexate may be decreased by 2.5 or 5.0 mg weekly (the minimum dose to stay in the study is 10 mg/week).
    Placebo Comparator: 3

    Drug: Placebo
    Subcutaneous (SC), once weekly from week 36 to week 88.

    Drug: Methotrexate
    Oral, 15 to 25 mg (varying based on dosage the subject is receiving at the time of screening and may be increased at the discretion of the investigator through Week 28 to a maximum of 25 mg/week), once weekly for 88 weeks. If a subject experiences an adverse event (AE) during the study, Methotrexate may be decreased by 2.5 or 5.0 mg weekly (the minimum dose to stay in the study is 10 mg/week).

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Achieving 28 Joint Disease Activity Score (DAS28) Less Than or Equal to (≤) 3.2 at Week 88 [Week 88]

      DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joint count (less than [<]20 percent [%] missing SJC or PJC was prorated), erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and Patient's General Health Visual Analog Scale (VAS). VAS is a line 0-100 millimeters (mm) in length; ranged from 0 (very well)-100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units equals (=) low disease activity.

    Secondary Outcome Measures

    1. Percentage of Participants Achieving DAS28 Low Disease Activity or Remission at Baseline, Weeks 4, 8, 12, 20, 28 and 36 [Baseline, Weeks 4, 8, 12, 20, 28, 36]

      DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units = low disease activity, DAS28 < 2.6 units = remission.

    2. Percentage of Participants Achieving DAS28 Low Disease Activity or Remission [Weeks 36, 40, 48, 56, 64, 72, 80 and 88]

      DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units = low disease activity, DAS28 < 2.6 units = remission.

    3. Change From Baseline in DAS28 at Weeks 4, 8, 12, 20, 28 and 36 [Baseline, Weeks 4, 8, 12, 20, 28 and 36]

      The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (>5.1=high disease activity; <=3.2=low disease activity; <2.6=remission); a continuous variable which is a composite of 4 variables (the number of tender joints out of 28, the number of swollen joints out of 28 joints, erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PGA) of disease activity measured on a visual analogue scale (VAS) of 100 mm). Change equals (=) Week X observation minus (-) Baseline observation.

    4. Change From Week 36 in DAS28 at Weeks 40, 48, 56, 64, 72, 80 and 88 [Weeks 36, 40, 48, 56, 64, 72, 80 and 88]

      The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (>5.1=high disease activity; <=3.2=low disease activity; <2.6=remission); a continuous variable which is a composite of 4 variables (the number of tender joints out of 28, the number of swollen joints out of 28 joints, ESR mm/hour and PGA of disease activity measured on a VAS of 100 mm). Change = Week X observation - Week 36 observation.

    5. Time to Loss of Low Disease Activity DAS28 and a Change of ≥ 0.6 Units in the DAS28 [Week 36 up to Week 88]

      DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. Low disease activity = DAS28 ≤ 3.2 units. DAS28 > 3.2 to 5.1 units = moderate to high disease activity.

    6. Time to Loss of Low Disease Activity DAS28 [Week 36 up to Week 88]

      DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units = low disease activity, DAS28 greater than (>)3.2 to 5.1 units = moderate to high disease activity.

    7. Proportion of Time Participants Had Low Disease Activity DAS28 Week 36 to Week 88 [Week 36 up to Week 88]

      DAS28 calculated from the number of SJC and PJC using the 28 joints, the ESR mm/hour and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 < 3.2 units = low disease activity. Cumulative proportion calculated as time-averaged Area Under the Curve (AUC) (AUC divided by number of weeks at that time point), with AUC calculated from Week 36 and Week 88.

    8. Change From Baseline in Prorated Swollen Joint Count at Weeks 4, 8, 12, 20, 28 and 36 [Baseline, Weeks 4, 8, 12, 20, 28 and 36]

      American College of Rheumatology (ACR), swollen joint count were an assessment of 28 joints. Joints are classified as either swollen or not swollen. If < 20% of swollen joints missing then total swollen joint prorated (multiplied by 28 divided by (/) number of non-missing swollen joints). Total possible score ranged from -28 to 28. An increase in swollen joints from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - baseline observation.

    9. Prorated Swollen Joint Count at Week 36 [Week 36]

      ACR, swollen joint count was an assessment of 28 joints. Joints were classified as either swollen or not swollen. If < 20% of swollen joints missing then total swollen joint prorated (multiplied by 28 divided by number of non-missing swollen joints). Total possible score of swollen joints ranged from 0-28.

    10. Change From Week 36 in Prorated Swollen Joint Count at Weeks 40, 48, 56, 64, 72, 80 and 88 [Week 36, Weeks 40, 48, 56, 64, 72, 80 and 88]

      ACR, swollen joint count was an assessment of 28 joints. Joints were classified as either swollen or not swollen. If < 20% of swollen joints missing then total swollen joint prorated (multiplied by 28 divided by (/) number of non-missing swollen joints). Total possible score ranged from -28 to 28. An increase in swollen joints from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - Week 36 observation.

    11. Change From Baseline in the Painful Joint Count at Weeks 4, 8, 12, 20, 28 and 36 [Baseline, Weeks 4, 8, 12, 20, 28 and 36]

      A total of 28 joints were assessed by the investigator using criteria based on pressure and joint manipulation. Total possible scores ranged from -28 to 28. An increase in joint pain count from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - Baseline observation.

    12. Painful Joint Count at Week 36 [Week 36]

      A total of 28 joints were assessed by the investigator using criteria based on pressure and joint manipulation. Total possible score ranged form 0-28.

    13. Change From Week 36 in Painful Joint Count at Weeks 40, 48, 56, 64, 72, 80 and 88 [Weeks 36 40, 48, 56, 64, 72, 80 and 88]

      Total of 28 joints were assessed by the investigator using criteria based on pressure and joint manipulation. Total possible scores ranged from -28 to 28. An increase in joint pain count from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - Week 36 observation.

    14. Change From Baseline in the Physician Global Assessment (PGA) at Weeks 4, 8, 12, 20, 28 and 36 [Baseline, Weeks 4, 8, 12, 20, 28 and 36]

      PGA of Disease Activity was measured on a 0 to 10 Scale, with 0 = no disease activity and 10 = extreme disease activity. Change = Week X observation - Baseline observation.

    15. PGA Score at Week 36 [Week 36]

      PGA of Disease Activity was measured on a 0 to 10 Scale, with 0 = no disease activity and 10 = extreme disease activity.

    16. Change From Week 36 in the PGA Score at Weeks 40, 48, 56, 64, 72, 80 and 88 [Weeks 36, 40, 48, 56, 64, 72, 80 and 88]

      PGA of Disease Activity was measured on a 0 to 10 Scale, with 0 = no disease activity and 10 = extreme disease activity. Change = Week X observation - Week 36 observation.

    17. Change From Baseline in Patient's Global Assessment (PtGA) of Arthritis Pain at Weeks 4, 8, 12, 20, 28 and 36 [Baseline, Weeks 4, 8, 12, 20, 28 and 36]

      Participants asked to rate their overall arthritis activity by circling a number ranging from 0 (no disease activity) to 10 (extreme disease activity). Change = Week X observation - Baseline observation.

    18. PtGA of Arthritis Pain at Week 36 [Week 36]

      PtGA asked the participant to assess their overall arthritis activity. Participants responded by circling a number ranging from 0 (no disease activity) to 10 (extreme disease activity).

    19. Change From Week 36 in PtGA of Arthritis Pain at Weeks 40, 48, 56, 64, 72, 80, 88 [Weeks 36, 40, 48, 56, 64, 72, 80, 88]

      PtGA asked the participant to assess their overall arthritis activity. Participants responded by circling a number ranging from 0 (no disease activity) to 10 (extreme disease activity). Change = Week X observation - Week 36 observation.

    20. Change From Baseline in Duration of Morning Stiffness at Weeks 4, 8, 12, 20, 28 and 36 [Baseline, Weeks 4, 8, 12, 20, 28 and 36]

      Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and when the participants were able to resume normal activities without stiffness. No stiffness present = 0; stiffness persisted the entire day = 1440 minutes (24 hour times [*] 60 min) was recorded. Change = Week X observation - Baseline observation.

    21. Duration of Morning Stiffness at Week 36 [Week 36]

      Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and when the participants were able to resume normal activities without stiffness. No stiffness present = 0; stiffness persisted the entire day = 1440 minutes (24 hour * 60 min) was recorded.

    22. Change From Week 36 in Duration of Morning Stiffness at Weeks 40, 48, 56, 64, 72, 80, 88 [Weeks 36, 40, 48, 56, 64, 72, 80, 88]

      Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness. No stiffness present = 0; stiffness persisted the entire day = 1440 minutes (24 hour * 60 min) was recorded. Change = Week X observation - Week 36 observation.

    23. Change From Baseline in General Health at Weeks 4, 8, 12, 20, 28 and 36 [Baseline, Weeks 4, 8, 12, 20, 28 and 36]

      General Health VAS is a 100 millimeter (mm) line marked by the participant. Participants were asked, "In general how would you rate your health over the last 2 to 3 weeks?" Scores ranged from 0 mm = very well to 100 mm = extremely bad. Change = Week X observation - Baseline observation.

    24. General Health at Week 36 [Week 36]

      General Health VAS is a 100 mm line marked by the participant. Participants are asked, "In general how would you rate your health over the last 2 to 3 weeks?" Scores ranged from 0 mm = very well to 100 mm = extremely bad.

    25. Change From Week 36 in General Health at Weeks 40, 48, 56, 64, 72, 80, 88 [Weeks 36, 40, 48, 56, 64, 72, 80, 88]

      General Health VAS is a 100 mm line marked by the participant. Participants were asked, "In general how would you rate your health over the last 2 to 3 weeks?" Scores ranged from 0 mm = very well to 100 mm = extremely bad. Change = Week X observation - Week 36 observation.

    26. Change From Baseline in Pain at Weeks 4, 8, 12, 20, 28 and 36 [Baseline, Weeks 4, 8, 12, 20, 28 and 36]

      100 mm line (Visual Analog Scale) marked by participant. Intensity of pain range (over past 2 to 3 days): 0 = no pain to 100 = worst possible pain. Change = Week X observation - Baseline observation.

    27. Pain at Week 36 [Week 36]

      100 mm line (Visual Analog Scale) marked by participant. Intensity of pain range (over past 2 to 3 days): 0 = no pain to 100 = pain as bad as it could be. Change = Week x observation minus (-) Baseline observation.

    28. Change From Week 36 in Pain at Weeks 40, 48, 56, 64, 72, 80 and 88 [Weeks 36, 40, 48, 56, 64, 72, 80 and 88]

      100 mm line (Visual Analog Scale) marked by participant. Intensity of pain range (over past 2 to 3 days): 0 = no pain to 100 = worst possible pain. Change = Week X observation - Week 36 observation.

    29. Percentage of Participants Achieving an Acceptable State on the Patient Acceptable Symptom State (PASS) at Baseline and Week 36 [Baseline, Week 36]

      PASS was a 1 question assessment of how rheumatoid arthritis has affected the participant in the last 2 days (If you were to remain in the next few months as you were during the last 2 days, would this be acceptable or unacceptable to you?).

    30. Percentage of Participants Achieving an Acceptable State on the PASS at Week 36 and Weeks 64 and 88 [Weeks 36, 64 and 88]

      PASS was a 1 question assessment of how rheumatoid arthritis has affected the participant in the last 2 days (If you were to remain in the next few months as you were during the last 2 days, would this be acceptable or unacceptable to you?).

    31. Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good or Moderate Response at Weeks 4, 8, 12, 20, 28 and 36 [Weeks 4, 8, 12, 20, 28 and 36]

      EULAR Response Criteria: Good response was defined as >1.2 units improvement in DAS28 from Baseline and DAS28 attained up to Week 88 of <=3.2 units. Non responders were participants with improvement of <0.6 units or participants with improvement of 0.6 to 1.2 units and DAS28 attained up to Week 88 of > 5.1 units. Remaining participants were defined as having a moderate response. Scores of good and moderate were considered to have therapeutic response.

    32. Percentage of Participants Achieving EULAR Good or Moderate Response at Week 36, 40, 48, 56, 64, 72, 80 and 88 [Week 36, 40, 48, 56, 64, 72, 80 and 88]

      EULAR Response Criteria: Good response was defined as >1.2 units improvement in DAS28 from Baseline and DAS28 attained up to Week 88 of <=3.2 units. Non responders were participants with improvement of <0.6 units or participants with improvement of 0.6 to 1.2 units and DAS28 attained up to Week 88 of > 5.1 units. Remaining participants were defined as having a moderate response. Scores of good and moderate were considered to have therapeutic response.

    33. Percentage of Participants With an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 4, 8, 12, 20, 28 and 36 [Weeks 4, 8, 12, 20, 28 and 36]

      ACR20 response, ≥ 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and = at least 20% improvement in at least 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant (ESR).

    34. Percentage of Participants With an ACR20 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88 [Weeks 36, 40, 48, 56, 64, 72, 80 and 88]

      ACR20 response: ≥ 20% improvement in tender joint count; ≥20% improvement in swollen joint count; and = at least 20% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).

    35. Percentage of Participants With an ACR50 Response at Weeks 4, 8, 12, 20, 28 and 36 [Weeks 4, 8, 12, 20, 28 and 36]

      ACR50 response: ≥ 50% improvement in tender joint count; = ≥50% improvement in swollen joint count; and = at least 50% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).

    36. Percentage of Participants With an ACR50 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88 [Weeks 36, 40, 48, 56, 64, 72, 80 and 88]

      ACR50 response: ≥ 50% improvement in tender joint count; = ≥50% improvement in swollen joint count; and = at least 50% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).

    37. Percentage of Participants With an ACR70 Response at Weeks 4, 8, 12, 20, 28 and 36 [Weeks 4, 8, 12, 20, 28 and 36]

      ACR70 response: ≥ 70% improvement in tender joint count; = ≥70% improvement in swollen joint count; and = at least 70% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).

    38. Percentage of Participants With an ACR70 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88 [Weeks 36, 40, 48, 56, 64, 72, 80 and 88]

      ACR70 response: ≥ 70% improvement in tender joint count; = ≥70% improvement in swollen joint count; and = at least 70% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and C-Reactive Protein CRP.

    39. Percentage of Participants With an ACR90 Response at Weeks 4, 8, 12, 20, 28 and 36 [Weeks 4, 8, 12, 20, 28 and 36]

      ACR90 response: ≥ 90% improvement in tender joint count; = ≥90% improvement in swollen joint count; and = at least 90% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).

    40. Percentage of Participants With an ACR90 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88 [Weeks 36, 40, 48, 56, 64, 72, 80 and 88]

      ACR90 response: ≥ 90% improvement in tender joint count; = 90% improvement in swollen joint count; and = 90% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).

    41. DAS28 at Week 36 [Week 36]

      The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (>5.1=high disease activity; <=3.2=low disease activity; <2.6=remission); a continuous variable which is a composite of 4 variables (the number of tender joints out of 28, the number of swollen joints out of 28 joints, ESR mm/hour and PGA of disease activity measured on a VAS of 100 mm).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Diagnosis of rheumatoid arthritis.

    • Currently receiving an optimal dose of oral Methotrexate (MTX)(at least 15 mg/week but no more than 25 mg/week) for the treatment of rheumatoid arthritis.

    • Active rheumatoid arthritis at the time of screening.

    Exclusion Criteria:

    • Previous or current treatment with etanercept, other tumor necrosis factor-alpha (TNF) inhibitors, or other biologic agents.

    • Concurrent treatment with any disease-modifying anti-rheumatoid drugs (DMARD), other than MTX within 28 days before baseline.

    • Concurrent treatment with more than 1 non-steroid anti-inflammatory drug (NSAID) at baseline.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pfizer Investigational Site Campsie New South Wales Australia 2194
    2 Pfizer Investigational Site Kogarah New South Wales Australia 2217
    3 Pfizer Investigational Site Maroochydore Queensland Australia 4558
    4 Pfizer Investigational Site Daw Park South Australia Australia 5041
    5 Pfizer Investigational Site Heidelberg West Victoria Australia 3081
    6 Pfizer Investigational Site Malvern Victoria Australia 3145
    7 Pfizer Investigational Site Victoria Park Australia 6100
    8 Pfizer Investigational Site Wien Austria 1130
    9 Pfizer Investigational Site Bruxelles Belgium 1200
    10 Pfizer Investigational Site Liege Belgium 4000
    11 Pfizer Investigational Site Yvoir Belgium 5530
    12 Pfizer Investigational Site Santiago Region Metropolitana Chile
    13 Pfizer Investigational Site Barranquilla Atlantico Colombia
    14 Pfizer Investigational Site Bogota Cundinamarca Colombia
    15 Pfizer Investigational Site Brno Czech Republic 656 91
    16 Pfizer Investigational Site Bruntal Czech Republic 792 01
    17 Pfizer Investigational Site Bruntal Czech Republic 79201
    18 Pfizer Investigational Site Praha 2 Czech Republic 128 50
    19 Pfizer Investigational Site Praha 5 Czech Republic 150 06
    20 Pfizer Investigational Site Zlin Czech Republic 760 01
    21 Pfizer Investigational Site Belgrade Former Serbia and Montenegro 11000
    22 Pfizer Investigational Site Niska Banja Former Serbia and Montenegro 18205
    23 Pfizer Investigational Site Corbeil-Essonnes France 91100
    24 Pfizer Investigational Site Le Kremlin Bicetre France 94270
    25 Pfizer Investigational Site Le Mans France 72037
    26 Pfizer Investigational Site Montpellier France 34059
    27 Pfizer Investigational Site Nice France 06202
    28 Pfizer Investigational Site Paris France 75018
    29 Pfizer Investigational Site Strasbourg France 67098
    30 Pfizer Investigational Site Toulouse France 31059
    31 Pfizer Investigational Site Berlin Germany 10117
    32 Pfizer Investigational Site Hamburg-Eilbek Germany 22081
    33 Pfizer Investigational Site Koeln Germany 50937
    34 Pfizer Investigational Site Leipzig Germany 04103
    35 Pfizer Investigational Site Leipzig Germany 4103
    36 Pfizer Investigational Site Wuerzburg Germany 97080
    37 Pfizer Investigational Site Budapest Hungary 1023
    38 Pfizer Investigational Site Debrecen Hungary 4012
    39 Pfizer Investigational Site Debrecen Hungary H-4032
    40 Pfizer Investigational Site Szombathely Hungary 9701
    41 Pfizer Investigational Site Catania CT Italy 95100
    42 Pfizer Investigational Site Orbassano TO Italy 10043
    43 Pfizer Investigational Site Roma Italy 00128
    44 Pfizer Investigational Site Seo-gu Daejeon Korea, Republic of 302-799
    45 Pfizer Investigational Site Namdong-gu Incheon Korea, Republic of 405-760
    46 Pfizer Investigational Site Seoul Korea Korea, Republic of 135-720
    47 Pfizer Investigational Site Seongdong-gu Seoul Korea, Republic of 133-792
    48 Pfizer Investigational Site Anyang-si Gyeonggi-do Korea, Republic of 431-070
    49 Pfizer Investigational Site Seoul Korea, Republic of 134-701
    50 Pfizer Investigational Site Seoul Korea, Republic of 143-729
    51 Pfizer Investigational Site Merida Yucatan Mexico 97000
    52 Pfizer Investigational Site Guadalajara Mexico 44650
    53 Pfizer Investigational Site Mexico City Mexico 06700
    54 Pfizer Investigational Site Mexico DF Mexico 11500
    55 Pfizer Investigational Site Monterrey Mexico 64020
    56 Pfizer Investigational Site Queretaro Mexico 76000
    57 Pfizer Investigational Site Heerlen Netherlands 6419 PC
    58 Pfizer Investigational Site Bydgoszcz Poland 85-168
    59 Pfizer Investigational Site Lodz Poland 93-513
    60 Pfizer Investigational Site Lublin Poland 20-954
    61 Pfizer Investigational Site Szczecin Poland 71-252
    62 Pfizer Investigational Site Warszawa Poland
    63 Pfizer Investigational Site Moscow Russian Federation 115522
    64 Pfizer Investigational Site Moscow Russian Federation 119002
    65 Pfizer Investigational Site Moscow Russian Federation 129110
    66 Pfizer Investigational Site Moscow Russian Federation
    67 Pfizer Investigational Site St Petersburg Russian Federation 199004
    68 Pfizer Investigational Site St. Petersburg Russian Federation 194291
    69 Pfizer Investigational Site Santiago de Compostela A Coruña Spain 157 06
    70 Pfizer Investigational Site Sabadell Barcelona Spain 08208
    71 Pfizer Investigational Site Barcelona Spain 08036
    72 Pfizer Investigational Site La Coruña Spain 15006
    73 Pfizer Investigational Site Malaga Spain 29009
    74 Pfizer Investigational Site Sevilla Spain 41009
    75 Pfizer Investigational Site Falun Sweden 79182
    76 Pfizer Investigational Site Oskarström Sweden 31392
    77 Pfizer Investigational Site Tapei City ROC Taiwan 114
    78 Pfizer Investigational Site Kaohsiung City Taiwan 807
    79 Pfizer Investigational Site Wigan Lancashire United Kingdom WN6 9EP
    80 Pfizer Investigational Site Dudley West Midlands United Kingdom DY1 2HQ

    Sponsors and Collaborators

    • Pfizer

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT00565409
    Other Study ID Numbers:
    • 0881A1-4423
    • B1801003
    First Posted:
    Nov 30, 2007
    Last Update Posted:
    Aug 10, 2015
    Last Verified:
    Aug 1, 2015
    Keywords provided by Pfizer
    Active Rheumatoid Arthritis
    Additional relevant MeSH terms:
    Arthritis
    Arthritis, Rheumatoid
    Etanercept
    Methotrexate

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1 Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants received etanercept (ETN) 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks. Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) less than or equal to (≤) 3.2 at Week 36 and an average DAS28 less than or equal to (≤) 3.2 from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ 3.2 from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ 3.2 from Week 12 visit through Week 36.
    Period Title: Period 1 Open Label
    STARTED 834 0 0 0
    COMPLETED 756 0 0 0
    NOT COMPLETED 78 0 0 0
    Period Title: Period 1 Open Label
    STARTED 756 0 0 0
    COMPLETED 604 0 0 0
    NOT COMPLETED 152 0 0 0
    Period Title: Period 1 Open Label
    STARTED 0 202 202 200
    COMPLETED 0 181 175 141
    NOT COMPLETED 0 21 27 59

    Baseline Characteristics

    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Overall Participants 834
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    48.36
    (11.94)
    Sex: Female, Male (Count of Participants)
    Female
    694
    83.2%
    Male
    140
    16.8%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Achieving 28 Joint Disease Activity Score (DAS28) Less Than or Equal to (≤) 3.2 at Week 88
    Description DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joint count (less than [<]20 percent [%] missing SJC or PJC was prorated), erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and Patient's General Health Visual Analog Scale (VAS). VAS is a line 0-100 millimeters (mm) in length; ranged from 0 (very well)-100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units equals (=) low disease activity.
    Time Frame Week 88

    Outcome Measure Data

    Analysis Population Description
    Modified Intent to Treat population (mITT): all participants who took at least 1 dose of double-blind test article and had at least 1 post-randomization DAS28 evaluation
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Number [percentage of participants]
    82.6
    9.9%
    79.1
    NaN
    42.6
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Sample size estimated based on moderate/severe rheumatoid arthritis(RA) trial. Study design included only moderate RA participants, thus a low disease activity estimate of 85% (ETN+MTX) vs 70% (MTX only) assumed, required 175 randomized participants in 3 treatments for a 90% power and Type I error of 0.05 to reject the null hypothesis of no ETN+MTX vs MTX only differences. More participants qualified for Period 2 than expected, Period 2 sample size roughly 15% larger than protocol-specified.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from Cochran-Mantel-Haenszel(CMH) test of general association, testing treatment effect on response. P-value and Odds Ratio (OR) stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments Loss of efficacy (LOE) imputation defined as LOE drop-outs were treated as non-responders/all other participants had LOCF applied as primary analysis.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.36
    Confidence Interval (2-Sided) 95%
    3.2 to 9.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3805
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments LOE imputation defined as LOE drop-outs were treated as non-responders and all other participants had LOCF applied as primary analysis.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.15
    Confidence Interval (2-Sided) 95%
    0.7 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments LOE imputation defined as LOE drop-outs were treated as non-responders and all other participants had LOCF applied as primary analysis.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.81
    Confidence Interval (2-Sided) 95%
    3.0 to 7.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants Achieving DAS28 Low Disease Activity or Remission at Baseline, Weeks 4, 8, 12, 20, 28 and 36
    Description DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units = low disease activity, DAS28 < 2.6 units = remission.
    Time Frame Baseline, Weeks 4, 8, 12, 20, 28, 36

    Outcome Measure Data

    Analysis Population Description
    Period 1 Modified Intent to Treat population (P1 mITT): all participants who took at least 1 dose of open-label test article; N=number of participants with evaluable data; Last observation carried forward (LOCF)
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 829
    Baseline-Low Disease Activity
    0.36
    0%
    Week 4-Low Disease Activity
    35.98
    4.3%
    Week 8-Low Disease Activity
    49.57
    5.9%
    Week 12-Low Disease Activity
    61.75
    7.4%
    Week 20-Low Disease Activity
    69.25
    8.3%
    Week 28-Low Disease Activity
    75.79
    9.1%
    Week 36-Low Disease Activity
    81.96
    9.8%
    Baseline-Remission
    0
    0%
    Week 4-Remission
    16.52
    2%
    Week 8-Remission
    28.83
    3.5%
    Week 12-Remission
    38.73
    4.6%
    Week 20-Remission
    45.52
    5.5%
    Week 28-Remission
    54.24
    6.5%
    Week 36-Remission
    63.56
    7.6%
    3. Secondary Outcome
    Title Percentage of Participants Achieving DAS28 Low Disease Activity or Remission
    Description DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units = low disease activity, DAS28 < 2.6 units = remission.
    Time Frame Weeks 36, 40, 48, 56, 64, 72, 80 and 88

    Outcome Measure Data

    Analysis Population Description
    Period 2 (P2) mITT
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Week 36-Low Disease Activity
    98.5
    11.8%
    99.0
    NaN
    100.0
    NaN
    Week 40-Low Disease Activity
    87.8
    10.5%
    84.3
    NaN
    65.4
    NaN
    Week 48-Low Disease Activity
    83.1
    10%
    81.1
    NaN
    53.3
    NaN
    Week 56-Low Disease Activity
    82.6
    9.9%
    81.1
    NaN
    44.7
    NaN
    Week 64-Low Disease Activity
    81.6
    9.8%
    82.1
    NaN
    48.7
    NaN
    Week 72-Low Disease Activity
    84.1
    10.1%
    82.6
    NaN
    45.7
    NaN
    Week 80-Low Disease Activity
    84.6
    10.1%
    81.6
    NaN
    45.7
    NaN
    Week 88-Low Disease Activity
    82.6
    9.9%
    80.6
    NaN
    45.2
    NaN
    Week 36-Remission
    81.1
    9.7%
    79.6
    NaN
    80.2
    NaN
    Week 40-Remission
    68.9
    8.3%
    63.5
    NaN
    42.6
    NaN
    Week 48-Remission
    65.7
    7.9%
    62.7
    NaN
    36.5
    NaN
    Week 56-Remission
    62.2
    7.5%
    65.2
    NaN
    28.9
    NaN
    Week 64-Remission
    63.7
    7.6%
    61.2
    NaN
    30.5
    NaN
    Week 72-Remission
    67.2
    8.1%
    65.2
    NaN
    27.9
    NaN
    Week 80-Remission
    67.2
    8.1%
    64.7
    NaN
    29.9
    NaN
    Week 88-Remission
    66.7
    8%
    60.2
    NaN
    29.4
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 36 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0853
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.11
    Confidence Interval (2-Sided) 95%
    0.5 to 21.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 36 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8491
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.96
    Confidence Interval (2-Sided) 95%
    0.2 to 4.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 36 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1278
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.97
    Confidence Interval (2-Sided) 95%
    0.4 to 42.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.63
    Confidence Interval (2-Sided) 95%
    2.1 to 6.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3027
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.43
    Confidence Interval (2-Sided) 95%
    0.8 to 2.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.51
    Confidence Interval (2-Sided) 95%
    1.5 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.55
    Confidence Interval (2-Sided) 95%
    2.7 to 7.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5871
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.18
    Confidence Interval (2-Sided) 95%
    0.7 to 2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.76
    Confidence Interval (2-Sided) 95%
    2.3 to 6.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 6.52
    Confidence Interval (2-Sided) 95%
    3.9 to 11.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6716
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.14
    Confidence Interval (2-Sided) 95%
    0.6 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.40
    Confidence Interval (2-Sided) 95%
    3.4 to 8.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.62
    Confidence Interval (2-Sided) 95%
    2.8 to 7.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9399
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.88
    Confidence Interval (2-Sided) 95%
    0.5 to 1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.78
    Confidence Interval (2-Sided) 95%
    3.0 to 7.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 6.25
    Confidence Interval (2-Sided) 95%
    3.7 to 10.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6692
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.08
    Confidence Interval (2-Sided) 95%
    0.6 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.46
    Confidence Interval (2-Sided) 95%
    3.4 to 8.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.74
    Confidence Interval (2-Sided) 95%
    3.4 to 9.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4326
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.20
    Confidence Interval (2-Sided) 95%
    0.7 to 2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.12
    Confidence Interval (2-Sided) 95%
    3.2 to 8.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.68
    Confidence Interval (2-Sided) 95%
    2.8 to 7.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6064
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.03
    Confidence Interval (2-Sided) 95%
    0.6 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88 Low Disease Activity
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.68
    Confidence Interval (2-Sided) 95%
    3.0 to 7.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 25
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 36 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4626
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.30
    Confidence Interval (2-Sided) 95%
    0.5 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 26
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 36 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2886
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.44
    Confidence Interval (2-Sided) 95%
    0.6 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 27
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 36 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7779
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.83
    Confidence Interval (2-Sided) 95%
    0.4 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 28
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.94
    Confidence Interval (2-Sided) 95%
    1.8 to 4.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 29
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2091
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.26
    Confidence Interval (2-Sided) 95%
    0.8 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 30
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.31
    Confidence Interval (2-Sided) 95%
    1.5 to 3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 31
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.33
    Confidence Interval (2-Sided) 95%
    2.1 to 5.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 32
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5351
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.11
    Confidence Interval (2-Sided) 95%
    0.7 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 33
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.12
    Confidence Interval (2-Sided) 95%
    2.0 to 4.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 34
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.09
    Confidence Interval (2-Sided) 95%
    2.6 to 6.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 35
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4574
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.86
    Confidence Interval (2-Sided) 95%
    0.5 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 36
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.04
    Confidence Interval (2-Sided) 95%
    3.2 to 8.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 37
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.19
    Confidence Interval (2-Sided) 95%
    2.7 to 6.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 38
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5229
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.14
    Confidence Interval (2-Sided) 95%
    0.7 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 39
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.84
    Confidence Interval (2-Sided) 95%
    2.5 to 6.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 40
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.36
    Confidence Interval (2-Sided) 95%
    3.3 to 8.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 41
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6464
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.15
    Confidence Interval (2-Sided) 95%
    0.7 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 42
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.79
    Confidence Interval (2-Sided) 95%
    3.0 to 7.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 43
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.96
    Confidence Interval (2-Sided) 95%
    3.1 to 7.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 44
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5499
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.13
    Confidence Interval (2-Sided) 95%
    0.7 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 45
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.11
    Confidence Interval (2-Sided) 95%
    2.6 to 6.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 46
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.41
    Confidence Interval (2-Sided) 95%
    2.8 to 7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 47
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1109
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.20
    Confidence Interval (2-Sided) 95%
    0.8 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 48
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88 Remission
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.85
    Confidence Interval (2-Sided) 95%
    2.5 to 6.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in DAS28 at Weeks 4, 8, 12, 20, 28 and 36
    Description The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (>5.1=high disease activity; <=3.2=low disease activity; <2.6=remission); a continuous variable which is a composite of 4 variables (the number of tender joints out of 28, the number of swollen joints out of 28 joints, erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PGA) of disease activity measured on a visual analogue scale (VAS) of 100 mm). Change equals (=) Week X observation minus (-) Baseline observation.
    Time Frame Baseline, Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; Last observation carried forward (LOCF); N=Number of participants with evaluable data
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 829
    Baseline
    4.37
    (0.02)
    Change at Week 4
    -0.88
    (0.03)
    Change at Week 8
    -1.22
    (0.03)
    Change at Week 12
    -1.45
    (0.03)
    Change at Week 20
    -1.60
    (0.03)
    Change at Week 28
    -1.72
    (0.04)
    Change at Week 36
    -1.89
    (0.04)
    5. Secondary Outcome
    Title Change From Week 36 in DAS28 at Weeks 40, 48, 56, 64, 72, 80 and 88
    Description The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (>5.1=high disease activity; <=3.2=low disease activity; <2.6=remission); a continuous variable which is a composite of 4 variables (the number of tender joints out of 28, the number of swollen joints out of 28 joints, ESR mm/hour and PGA of disease activity measured on a VAS of 100 mm). Change = Week X observation - Week 36 observation.
    Time Frame Weeks 36, 40, 48, 56, 64, 72, 80 and 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF; N=number of participants with evaluable data
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 196 197 188
    Change at Week 40
    0.30
    (0.06)
    0.31
    (0.06)
    0.84
    (0.06)
    Change at Week 48
    0.40
    (0.07)
    0.36
    (0.07)
    1.25
    (0.07)
    Change at Week 56
    0.44
    (0.07)
    0.37
    (0.07)
    1.35
    (0.07)
    Change at Week 64
    0.47
    (0.07)
    0.40
    (0.07)
    1.33
    (0.07)
    Change at Week 72
    0.35
    (0.08)
    0.38
    (0.08)
    1.40
    (0.08)
    Change at Week 80
    0.40
    (0.08)
    0.40
    (0.08)
    1.42
    (0.08)
    Change at Week 88
    0.39
    (0.08)
    0.50
    (0.08)
    1.44
    (0.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.54
    Confidence Interval (2-Sided) 95%
    -0.7 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9344
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.01
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.53
    Confidence Interval (2-Sided) 95%
    -0.7 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.84
    Confidence Interval (2-Sided) 95%
    -1.0 to -0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6173
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.05
    Confidence Interval (2-Sided) 95%
    -0.1 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.89
    Confidence Interval (2-Sided) 95%
    -1.1 to -0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.92
    Confidence Interval (2-Sided) 95%
    -1.1 to -0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5136
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.06
    Confidence Interval (2-Sided) 95%
    -0.1 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.98
    Confidence Interval (2-Sided) 95%
    -1.2 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.86
    Confidence Interval (2-Sided) 95%
    -1.1 to -0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4868
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.07
    Confidence Interval (2-Sided) 95%
    -0.1 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.93
    Confidence Interval (2-Sided) 95%
    -1.1 to -0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.05
    Confidence Interval (2-Sided) 95%
    -1.3 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7847
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.03
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.02
    Confidence Interval (2-Sided) 95%
    -1.2 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.02
    Confidence Interval (2-Sided) 95%
    -1.2 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9810
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.00
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.02
    Confidence Interval (2-Sided) 95%
    -1.2 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.04
    Confidence Interval (2-Sided) 95%
    -1.3 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3562
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.10
    Confidence Interval (2-Sided) 95%
    -0.3 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.94
    Confidence Interval (2-Sided) 95%
    -1.2 to -0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Time to Loss of Low Disease Activity DAS28 and a Change of ≥ 0.6 Units in the DAS28
    Description DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. Low disease activity = DAS28 ≤ 3.2 units. DAS28 > 3.2 to 5.1 units = moderate to high disease activity.
    Time Frame Week 36 up to Week 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT;Imputation of failure; observed cases
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Median (95% Confidence Interval) [days]
    NA
    NA
    85.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Imputation of failure defined as participants who did not reach the endpoint and discontinued due to lack of efficacy, with reason of unsatisfactory response-efficacy, adverse event, other or protocol violation were set to an event at time of discontinuation.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Week 88 censored data was censored at 372 days.
    Method Log Rank
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Imputation of failure defined as participants who did not reach the endpoint and discontinued due to lack of efficacy, with reason of unsatisfactory response-efficacy, adverse event, other or protocol violation were set to an event at time of discontinuation.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Week 88 censored data was censored at 372 days.
    Method Log Rank
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Imputation of failure defined as participants who did not reach the endpoint and discontinued due to lack of efficacy, with reason of unsatisfactory response-efficacy, adverse event, other or protocol violation were set to an event at time of discontinuation.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8622
    Comments Week 88 censored data was censored at 372 days.
    Method Log Rank
    Comments
    7. Secondary Outcome
    Title Time to Loss of Low Disease Activity DAS28
    Description DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units = low disease activity, DAS28 greater than (>)3.2 to 5.1 units = moderate to high disease activity.
    Time Frame Week 36 up to Week 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT;
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Median (95% Confidence Interval) [days]
    366.0
    NA
    85.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Week 88 censored data was censored at 372 days.
    Method Log Rank
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9841
    Comments Week 88 censored data was censored at 372 days.
    Method Log Rank
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Week 88 censored data was censored at 372 days.
    Method Log Rank
    Comments
    8. Secondary Outcome
    Title Proportion of Time Participants Had Low Disease Activity DAS28 Week 36 to Week 88
    Description DAS28 calculated from the number of SJC and PJC using the 28 joints, the ESR mm/hour and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 < 3.2 units = low disease activity. Cumulative proportion calculated as time-averaged Area Under the Curve (AUC) (AUC divided by number of weeks at that time point), with AUC calculated from Week 36 and Week 88.
    Time Frame Week 36 up to Week 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Mean (Standard Error) [proportion of weeks in DAS28 <3.2]
    0.85
    (0.02)
    0.84
    (0.02)
    0.58
    (0.02)
    9. Secondary Outcome
    Title Change From Baseline in Prorated Swollen Joint Count at Weeks 4, 8, 12, 20, 28 and 36
    Description American College of Rheumatology (ACR), swollen joint count were an assessment of 28 joints. Joints are classified as either swollen or not swollen. If < 20% of swollen joints missing then total swollen joint prorated (multiplied by 28 divided by (/) number of non-missing swollen joints). Total possible score ranged from -28 to 28. An increase in swollen joints from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - baseline observation.
    Time Frame Baseline, Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 830
    Baseline
    3.82
    (0.09)
    Change at Week 4
    -1.31
    (0.08)
    Change at Week 8
    -1.96
    (0.08)
    Change at Week 12
    -2.29
    (0.08)
    Change at Week 20
    -2.60
    (0.09)
    Change at Week 28
    -2.70
    (0.09)
    Change at Week 36
    -2.67
    (0.10)
    10. Secondary Outcome
    Title Prorated Swollen Joint Count at Week 36
    Description ACR, swollen joint count was an assessment of 28 joints. Joints were classified as either swollen or not swollen. If < 20% of swollen joints missing then total swollen joint prorated (multiplied by 28 divided by number of non-missing swollen joints). Total possible score of swollen joints ranged from 0-28.
    Time Frame Week 36

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Mean (Standard Error) [number of swollen joints]
    0.63
    (0.11)
    0.57
    (0.09)
    0.59
    (0.08)
    11. Secondary Outcome
    Title Change From Week 36 in Prorated Swollen Joint Count at Weeks 40, 48, 56, 64, 72, 80 and 88
    Description ACR, swollen joint count was an assessment of 28 joints. Joints were classified as either swollen or not swollen. If < 20% of swollen joints missing then total swollen joint prorated (multiplied by 28 divided by (/) number of non-missing swollen joints). Total possible score ranged from -28 to 28. An increase in swollen joints from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - Week 36 observation.
    Time Frame Week 36, Weeks 40, 48, 56, 64, 72, 80 and 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Change at Week 40
    0.10
    (0.11)
    0.14
    (0.11)
    0.91
    (0.11)
    Change at Week 48
    0.25
    (0.15)
    0.21
    (0.15)
    1.38
    (0.15)
    Change at Week 56
    0.28
    (0.16)
    0.26
    (0.16)
    1.49
    (0.16)
    Change at Week 64
    0.37
    (0.17)
    0.34
    (0.17)
    1.64
    (0.17)
    Change at Week 72
    0.20
    (0.16)
    0.22
    (0.16)
    1.64
    (0.17)
    Change at Week 80
    0.25
    (0.18)
    0.32
    (0.18)
    1.82
    (0.18)
    Change at Week 88
    0.17
    (0.18)
    0.49
    (0.18)
    1.92
    (0.18)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.81
    Confidence Interval (2-Sided) 95%
    -1.1 to -0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8015
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.04
    Confidence Interval (2-Sided) 95%
    -0.3 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.78
    Confidence Interval (2-Sided) 95%
    -1.1 to -0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.14
    Confidence Interval (2-Sided) 95%
    -1.5 to -0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8534
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.04
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.18
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.21
    Confidence Interval (2-Sided) 95%
    -1.7 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9074
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.03
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.24
    Confidence Interval (2-Sided) 95%
    -1.7 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.28
    Confidence Interval (2-Sided) 95%
    -1.8 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9229
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.02
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.30
    Confidence Interval (2-Sided) 95%
    -1.8 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.44
    Confidence Interval (2-Sided) 95%
    -1.9 to -1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9279
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.02
    Confidence Interval (2-Sided) 95%
    -0.5 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.42
    Confidence Interval (2-Sided) 95%
    -1.9 to -1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.58
    Confidence Interval (2-Sided) 95%
    -2.1 to -1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7695
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.07
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.50
    Confidence Interval (2-Sided) 95%
    -2.0 to -1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.75
    Confidence Interval (2-Sided) 95%
    -2.3 to -1.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2182
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.31
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.44
    Confidence Interval (2-Sided) 95%
    -1.9 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title Change From Baseline in the Painful Joint Count at Weeks 4, 8, 12, 20, 28 and 36
    Description A total of 28 joints were assessed by the investigator using criteria based on pressure and joint manipulation. Total possible scores ranged from -28 to 28. An increase in joint pain count from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - Baseline observation.
    Time Frame Baseline, Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 830
    Baseline
    5.09
    (0.10)
    Change at Week 4
    -1.68
    (0.10)
    Change at Week 8
    -2.50
    (0.10)
    Change at Week 12
    -2.86
    (0.11)
    Change at Week 20
    -3.11
    (0.12)
    Change at Week 28
    -3.32
    (0.12)
    Change at Week 36
    -3.51
    (0.13)
    13. Secondary Outcome
    Title Painful Joint Count at Week 36
    Description A total of 28 joints were assessed by the investigator using criteria based on pressure and joint manipulation. Total possible score ranged form 0-28.
    Time Frame Week 36

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Mean (Standard Error) [number of painful joints]
    0.64
    (0.08)
    0.69
    (0.09)
    0.74
    (0.09)
    14. Secondary Outcome
    Title Change From Week 36 in Painful Joint Count at Weeks 40, 48, 56, 64, 72, 80 and 88
    Description Total of 28 joints were assessed by the investigator using criteria based on pressure and joint manipulation. Total possible scores ranged from -28 to 28. An increase in joint pain count from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - Week 36 observation.
    Time Frame Weeks 36 40, 48, 56, 64, 72, 80 and 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 196 197 188
    Change at Week 40
    0.61
    (0.17)
    0.49
    (0.17)
    1.47
    (0.17)
    Change at Week 48
    0.67
    (0.21)
    0.63
    (0.21)
    2.69
    (0.21)
    Change at Week 56
    0.61
    (0.20)
    0.66
    (0.20)
    2.67
    (0.21)
    Change at Week 64
    0.79
    (0.22)
    0.73
    (0.22)
    2.76
    (0.22)
    Change at Week 72
    0.63
    (0.23)
    0.78
    (0.23)
    3.01
    (0.23)
    Change at Week 80
    0.74
    (0.23)
    0.88
    (0.23)
    3.02
    (0.23)
    Change at Week 88
    0.73
    (0.24)
    0.78
    (0.24)
    3.14
    (0.24)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0003
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.86
    Confidence Interval (2-Sided) 95%
    -1.3 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6088
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.12
    Confidence Interval (2-Sided) 95%
    -0.3 to 0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.98
    Confidence Interval (2-Sided) 95%
    -1.4 to -0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.02
    Confidence Interval (2-Sided) 95%
    -2.6 to -1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9048
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.04
    Confidence Interval (2-Sided) 95%
    -0.5 to 0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.06
    Confidence Interval (2-Sided) 95%
    -2.6 to -1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.06
    Confidence Interval (2-Sided) 95%
    -2.6 to -1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8437
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.06
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.00
    Confidence Interval (2-Sided) 95%
    -2.6 to -1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.98
    Confidence Interval (2-Sided) 95%
    -2.6 to -1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8587
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.06
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.03
    Confidence Interval (2-Sided) 95%
    -2.6 to -1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.38
    Confidence Interval (2-Sided) 95%
    -3.0 to -1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6323
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.15
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.23
    Confidence Interval (2-Sided) 95%
    -2.9 to -1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.28
    Confidence Interval (2-Sided) 95%
    -2.9 to -1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6558
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.15
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.14
    Confidence Interval (2-Sided) 95%
    -2.8 to -1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.41
    Confidence Interval (2-Sided) 95%
    -3.1 to -1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8688
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.06
    Confidence Interval (2-Sided) 95%
    -0.7 to 0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.35
    Confidence Interval (2-Sided) 95%
    -3.0 to -1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Secondary Outcome
    Title Change From Baseline in the Physician Global Assessment (PGA) at Weeks 4, 8, 12, 20, 28 and 36
    Description PGA of Disease Activity was measured on a 0 to 10 Scale, with 0 = no disease activity and 10 = extreme disease activity. Change = Week X observation - Baseline observation.
    Time Frame Baseline, Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 833
    Baseline
    4.11
    (0.05)
    Change at Week 4
    -1.29
    (0.05)
    Change at Week 8
    -1.84
    (0.06)
    Change at Week 12
    -2.09
    (0.06)
    Change at Week 20
    -2.26
    (0.06)
    Change at Week 28
    -2.45
    (0.06)
    Change at Week 36
    -2.57
    (0.06)
    16. Secondary Outcome
    Title PGA Score at Week 36
    Description PGA of Disease Activity was measured on a 0 to 10 Scale, with 0 = no disease activity and 10 = extreme disease activity.
    Time Frame Week 36

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Mean (Standard Error) [units on a scale]
    1.06
    (0.07)
    1.19
    (0.08)
    1.11
    (0.05)
    17. Secondary Outcome
    Title Change From Week 36 in the PGA Score at Weeks 40, 48, 56, 64, 72, 80 and 88
    Description PGA of Disease Activity was measured on a 0 to 10 Scale, with 0 = no disease activity and 10 = extreme disease activity. Change = Week X observation - Week 36 observation.
    Time Frame Weeks 36, 40, 48, 56, 64, 72, 80 and 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Change at Week 40
    0.25
    (0.09)
    0.24
    (0.09)
    0.98
    (0.09)
    Change at Week 48
    0.37
    (0.10)
    0.26
    (0.11)
    1.48
    (0.11)
    Change at Week 56
    0.37
    (0.10)
    0.34
    (0.10)
    1.49
    (0.11)
    Change at Week 64
    0.41
    (0.11)
    0.26
    (0.11)
    1.51
    (0.11)
    Change at Week 72
    0.32
    (0.11)
    0.24
    (0.11)
    1.57
    (0.11)
    Change at Week 80
    0.27
    (0.11)
    0.34
    (0.11)
    1.61
    (0.11)
    Change at Week 88
    0.23
    (0.11)
    0.35
    (0.12)
    1.67
    (0.12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.73
    Confidence Interval (2-Sided) 95%
    -1.0 to -0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9636
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.01
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.74
    Confidence Interval (2-Sided) 95%
    -1.0 to -0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.11
    Confidence Interval (2-Sided) 95%
    -1.4 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4605
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.11
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.22
    Confidence Interval (2-Sided) 95%
    -1.5 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.12
    Confidence Interval (2-Sided) 95%
    -1.4 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8404
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.03
    Confidence Interval (2-Sided) 95%
    -0.3 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.15
    Confidence Interval (2-Sided) 95%
    -1.4 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.10
    Confidence Interval (2-Sided) 95%
    -1.4 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3118
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.16
    Confidence Interval (2-Sided) 95%
    -0.1 to 0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.26
    Confidence Interval (2-Sided) 95%
    -1.6 to -1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.26
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6100
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.08
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.34
    Confidence Interval (2-Sided) 95%
    -1.6 to -1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.34
    Confidence Interval (2-Sided) 95%
    -1.6 to -1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6552
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.07
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.27
    Confidence Interval (2-Sided) 95%
    -1.6 to -1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.43
    Confidence Interval (2-Sided) 95%
    -1.8 to -1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4753
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.12
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.32
    Confidence Interval (2-Sided) 95%
    -1.6 to -1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    18. Secondary Outcome
    Title Change From Baseline in Patient's Global Assessment (PtGA) of Arthritis Pain at Weeks 4, 8, 12, 20, 28 and 36
    Description Participants asked to rate their overall arthritis activity by circling a number ranging from 0 (no disease activity) to 10 (extreme disease activity). Change = Week X observation - Baseline observation.
    Time Frame Baseline, Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 832
    Baseline
    4.85
    (0.06)
    Change at Week 4
    -1.16
    (0.06)
    Change at Week 8
    -1.46
    (0.07)
    Change at Week 12
    -1.68
    (0.07)
    Change at Week 20
    -2.01
    (0.07)
    Change at Week 28
    -2.14
    (0.08)
    Change at Week 36
    -2.46
    (0.08)
    19. Secondary Outcome
    Title PtGA of Arthritis Pain at Week 36
    Description PtGA asked the participant to assess their overall arthritis activity. Participants responded by circling a number ranging from 0 (no disease activity) to 10 (extreme disease activity).
    Time Frame Week 36

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Mean (Standard Error) [units on a scale]
    1.80
    (0.12)
    1.77
    (0.10)
    1.86
    (0.11)
    20. Secondary Outcome
    Title Change From Week 36 in PtGA of Arthritis Pain at Weeks 40, 48, 56, 64, 72, 80, 88
    Description PtGA asked the participant to assess their overall arthritis activity. Participants responded by circling a number ranging from 0 (no disease activity) to 10 (extreme disease activity). Change = Week X observation - Week 36 observation.
    Time Frame Weeks 36, 40, 48, 56, 64, 72, 80, 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Change at Week 40
    0.41
    (0.12)
    0.46
    (0.11)
    1.28
    (0.12)
    Change at Week 48
    0.36
    (0.12)
    0.54
    (0.12)
    1.76
    (0.13)
    Change at Week 56
    0.47
    (0.13)
    0.60
    (0.13)
    1.76
    (0.13)
    Change at Week 64
    0.45
    (0.13)
    0.60
    (0.13)
    1.75
    (0.13)
    Change at Week 72
    0.33
    (0.14)
    0.67
    (0.14)
    1.93
    (0.14)
    Change at Week 80
    0.15
    (0.13)
    0.57
    (0.13)
    1.70
    (0.13)
    Change at Week 88
    0.29
    (0.14)
    0.59
    (0.14)
    1.84
    (0.14)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.88
    Confidence Interval (2-Sided) 95%
    -1.2 to -0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7427
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.05
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.82
    Confidence Interval (2-Sided) 95%
    -1.1 to -0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.40
    Confidence Interval (2-Sided) 95%
    -1.7 to -1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3129
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.18
    Confidence Interval (2-Sided) 95%
    -0.5 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.23
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.29
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4645
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.13
    Confidence Interval (2-Sided) 95%
    -0.5 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.16
    Confidence Interval (2-Sided) 95%
    -1.5 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.30
    Confidence Interval (2-Sided) 95%
    -1.7 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3793
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.16
    Confidence Interval (2-Sided) 95%
    -0.5 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.14
    Confidence Interval (2-Sided) 95%
    -1.5 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.60
    Confidence Interval (2-Sided) 95%
    -2.0 to -1.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0816
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.34
    Confidence Interval (2-Sided) 95%
    -0.7 to 0.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.26
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.54
    Confidence Interval (2-Sided) 95%
    -1.9 to -1.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0256
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.42
    Confidence Interval (2-Sided) 95%
    -0.8 to -0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.13
    Confidence Interval (2-Sided) 95%
    -1.5 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.54
    Confidence Interval (2-Sided) 95%
    -1.9 to -1.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1158
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.30
    Confidence Interval (2-Sided) 95%
    -0.7 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.24
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    21. Secondary Outcome
    Title Change From Baseline in Duration of Morning Stiffness at Weeks 4, 8, 12, 20, 28 and 36
    Description Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and when the participants were able to resume normal activities without stiffness. No stiffness present = 0; stiffness persisted the entire day = 1440 minutes (24 hour times [*] 60 min) was recorded. Change = Week X observation - Baseline observation.
    Time Frame Baseline, Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 830
    Baseline
    176.98
    (333.51)
    Change at Week 4
    -81.31
    (335.75)
    Change at Week 8
    -80.73
    (342.65)
    Change at Week 12
    -90.64
    (380.18)
    Change at Week 20
    -101.75
    (378.01)
    Change at Week 28
    -97.85
    (377.65)
    Change at Week 36
    -112.36
    (358.94)
    22. Secondary Outcome
    Title Duration of Morning Stiffness at Week 36
    Description Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and when the participants were able to resume normal activities without stiffness. No stiffness present = 0; stiffness persisted the entire day = 1440 minutes (24 hour * 60 min) was recorded.
    Time Frame Week 36

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 200 201 196
    Mean (Standard Error) [min]
    34.60
    (10.35)
    36.46
    (8.13)
    38.03
    (10.84)
    23. Secondary Outcome
    Title Change From Week 36 in Duration of Morning Stiffness at Weeks 40, 48, 56, 64, 72, 80, 88
    Description Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness. No stiffness present = 0; stiffness persisted the entire day = 1440 minutes (24 hour * 60 min) was recorded. Change = Week X observation - Week 36 observation.
    Time Frame Weeks 36, 40, 48, 56, 64, 72, 80, 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 200 201 196
    Change at Week 40
    3.43
    (12.82)
    14.00
    (12.60)
    45.10
    (12.83)
    Change at Week 48
    -7.64
    (14.47)
    35.54
    (14.47)
    72.41
    (14.62)
    Change at Week 56
    -2.10
    (14.19)
    24.04
    (14.19)
    87.09
    (14.34)
    Change at Week 64
    13.80
    (16.09)
    15.65
    (16.10)
    98.16
    (16.26)
    Change at Week 72
    8.30
    (17.36)
    18.50
    (17.37)
    117.04
    (17.54)
    Change at Week 80
    -1.06
    (15.18)
    12.63
    (15.18)
    114.42
    (15.34)
    Change at Week 88
    24.54
    (16.29)
    12.23
    (16.30)
    96.14
    (16.46)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0214
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -41.67
    Confidence Interval (2-Sided) 95%
    -77.1 to -6.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5544
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -10.57
    Confidence Interval (2-Sided) 95%
    -45.6 to 24.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0826
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -31.10
    Confidence Interval (2-Sided) 95%
    -66.2 to 4.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -80.05
    Confidence Interval (2-Sided) 95%
    -120.3 to -39.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0344
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -43.18
    Confidence Interval (2-Sided) 95%
    -83.2 to -3.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0721
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -36.87
    Confidence Interval (2-Sided) 95%
    -77.1 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -89.19
    Confidence Interval (2-Sided) 95%
    -128.7 to -49.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1910
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -26.14
    Confidence Interval (2-Sided) 95%
    -65.4 to 13.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0018
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -63.05
    Confidence Interval (2-Sided) 95%
    -102.5 to -23.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -84.36
    Confidence Interval (2-Sided) 95%
    -129.1 to -39.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9350
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.85
    Confidence Interval (2-Sided) 95%
    -46.3 to 42.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0003
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -82.52
    Confidence Interval (2-Sided) 95%
    -127.2 to -37.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -108.73
    Confidence Interval (2-Sided) 95%
    -157.0 to -60.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6764
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -10.20
    Confidence Interval (2-Sided) 95%
    -58.2 to 37.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -98.53
    Confidence Interval (2-Sided) 95%
    -146.7 to -50.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -115.48
    Confidence Interval (2-Sided) 95%
    -157.7 to -73.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5219
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -13.69
    Confidence Interval (2-Sided) 95%
    -55.6 to 28.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -101.80
    Confidence Interval (2-Sided) 95%
    -144.0 to -59.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0020
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -71.60
    Confidence Interval (2-Sided) 95%
    -116.9 to -26.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5917
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 12.30
    Confidence Interval (2-Sided) 95%
    -32.7 to 57.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0003
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -83.91
    Confidence Interval (2-Sided) 95%
    -129.2 to -38.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    24. Secondary Outcome
    Title Change From Baseline in General Health at Weeks 4, 8, 12, 20, 28 and 36
    Description General Health VAS is a 100 millimeter (mm) line marked by the participant. Participants were asked, "In general how would you rate your health over the last 2 to 3 weeks?" Scores ranged from 0 mm = very well to 100 mm = extremely bad. Change = Week X observation - Baseline observation.
    Time Frame Baseline, Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 832
    Baseline
    43.37
    (16.95)
    Change at Week 4
    -9.39
    (18.93)
    Change at Week 8
    -12.36
    (21.17)
    Change at Week 12
    -15.69
    (20.72)
    Change at Week 20
    -18.65
    (21.09)
    Change at Week 28
    -19.47
    (22.47)
    Change at Week 36
    -22.66
    (22.06)
    25. Secondary Outcome
    Title General Health at Week 36
    Description General Health VAS is a 100 mm line marked by the participant. Participants are asked, "In general how would you rate your health over the last 2 to 3 weeks?" Scores ranged from 0 mm = very well to 100 mm = extremely bad.
    Time Frame Week 36

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Mean (Standard Error) [mm]
    14.12
    (1.11)
    14.77
    (1.06)
    15.09
    (1.10)
    26. Secondary Outcome
    Title Change From Week 36 in General Health at Weeks 40, 48, 56, 64, 72, 80, 88
    Description General Health VAS is a 100 mm line marked by the participant. Participants were asked, "In general how would you rate your health over the last 2 to 3 weeks?" Scores ranged from 0 mm = very well to 100 mm = extremely bad. Change = Week X observation - Week 36 observation.
    Time Frame Weeks 36, 40, 48, 56, 64, 72, 80, 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 196
    Change at Week 40
    3.26
    (1.12)
    5.82
    (1.11)
    12.05
    (1.13)
    Change at Week 48
    4.67
    (1.19)
    5.36
    (1.20)
    16.76
    (1.21)
    Change at Week 56
    5.09
    (1.25)
    6.46
    (1.26)
    17.19
    (1.27)
    Change at Week 64
    4.04
    (1.22)
    5.36
    (1.22)
    16.87
    (1.23)
    Change at Week 72
    3.76
    (1.33)
    6.88
    (1.33)
    18.55
    (1.34)
    Change at Week 80
    2.70
    (1.28)
    4.59
    (1.28)
    17.26
    (1.29)
    Change at Week 88
    3.89
    (1.33)
    6.22
    (1.33)
    17.06
    (1.34)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.79
    Confidence Interval (2-Sided) 95%
    -11.9 to -5.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1033
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.55
    Confidence Interval (2-Sided) 95%
    -5.6 to 0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -6.23
    Confidence Interval (2-Sided) 95%
    -9.3 to -3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.09
    Confidence Interval (2-Sided) 95%
    -15.4 to -8.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6802
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.69
    Confidence Interval (2-Sided) 95%
    -4.0 to 2.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -11.39
    Confidence Interval (2-Sided) 95%
    -14.7 to -8.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.09
    Confidence Interval (2-Sided) 95%
    -15.6 to -8.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4404
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.36
    Confidence Interval (2-Sided) 95%
    -4.8 to 2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -10.73
    Confidence Interval (2-Sided) 95%
    -14.2 to -7.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.83
    Confidence Interval (2-Sided) 95%
    -16.2 to -9.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4437
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.32
    Confidence Interval (2-Sided) 95%
    -4.7 to 2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -11.51
    Confidence Interval (2-Sided) 95%
    -14.9 to -8.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -14.79
    Confidence Interval (2-Sided) 95%
    -18.5 to -11.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0960
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.12
    Confidence Interval (2-Sided) 95%
    -6.8 to 0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -11.67
    Confidence Interval (2-Sided) 95%
    -15.4 to -8.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -14.56
    Confidence Interval (2-Sided) 95%
    -18.1 to -11.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2948
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.88
    Confidence Interval (2-Sided) 95%
    -5.4 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.68
    Confidence Interval (2-Sided) 95%
    -16.2 to -9.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -13.16
    Confidence Interval (2-Sided) 95%
    -16.9 to -9.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2130
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.33
    Confidence Interval (2-Sided) 95%
    -6.0 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -10.83
    Confidence Interval (2-Sided) 95%
    -14.5 to -7.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    27. Secondary Outcome
    Title Change From Baseline in Pain at Weeks 4, 8, 12, 20, 28 and 36
    Description 100 mm line (Visual Analog Scale) marked by participant. Intensity of pain range (over past 2 to 3 days): 0 = no pain to 100 = worst possible pain. Change = Week X observation - Baseline observation.
    Time Frame Baseline, Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 832
    Baseline
    45.47
    (0.60)
    Change at Week 4
    -13.06
    (0.69)
    Change at Week 8
    -17.11
    (0.73)
    Change at Week 12
    -19.47
    (0.73)
    Change at Week 20
    -22.11
    (0.73)
    Change at Week 28
    -22.98
    (0.78)
    Change at Week 36
    -25.96
    (0.76)
    28. Secondary Outcome
    Title Pain at Week 36
    Description 100 mm line (Visual Analog Scale) marked by participant. Intensity of pain range (over past 2 to 3 days): 0 = no pain to 100 = pain as bad as it could be. Change = Week x observation minus (-) Baseline observation.
    Time Frame Week 36

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Mean (Standard Error) [mm]
    12.78
    (1.09)
    13.87
    (1.04)
    14.21
    (1.11)
    29. Secondary Outcome
    Title Change From Week 36 in Pain at Weeks 40, 48, 56, 64, 72, 80 and 88
    Description 100 mm line (Visual Analog Scale) marked by participant. Intensity of pain range (over past 2 to 3 days): 0 = no pain to 100 = worst possible pain. Change = Week X observation - Week 36 observation.
    Time Frame Weeks 36, 40, 48, 56, 64, 72, 80 and 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Change at Week 40
    4.50
    (1.15)
    4.91
    (1.15)
    13.05
    (1.17)
    Change at Week 48
    5.16
    (1.29)
    5.66
    (1.30)
    18.77
    (1.31)
    Change at Week 56
    5.23
    (1.29)
    6.25
    (1.29)
    17.76
    (1.30)
    Change at Week 64
    4.61
    (1.32)
    6.55
    (1.32)
    18.49
    (1.33)
    Change at Week 72
    4.26
    (1.37)
    7.05
    (1.37)
    19.90
    (1.38)
    Change at Week 80
    3.36
    (1.36)
    5.92
    (1.36)
    18.23
    (1.37)
    Change at Week 88
    3.88
    (1.37)
    6.31
    (1.37)
    18.57
    (1.39)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.55
    Confidence Interval (2-Sided) 95%
    -11.8 to -5.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8033
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.40
    Confidence Interval (2-Sided) 95%
    -3.6 to 2.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.14
    Confidence Interval (2-Sided) 95%
    -11.3 to -4.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -13.61
    Confidence Interval (2-Sided) 95%
    -17.2 to -10.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7830
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.50
    Confidence Interval (2-Sided) 95%
    -4.1 to 3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -13.11
    Confidence Interval (2-Sided) 95%
    -16.7 to -9.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.53
    Confidence Interval (2-Sided) 95%
    -16.1 to -8.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5732
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.02
    Confidence Interval (2-Sided) 95%
    -4.6 to 2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -11.50
    Confidence Interval (2-Sided) 95%
    -15.1 to -7.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -13.88
    Confidence Interval (2-Sided) 95%
    -17.6 to -10.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2972
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.94
    Confidence Interval (2-Sided) 95%
    -5.6 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -11.94
    Confidence Interval (2-Sided) 95%
    -15.6 to -8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -15.64
    Confidence Interval (2-Sided) 95%
    -19.4 to -11.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1477
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.80
    Confidence Interval (2-Sided) 95%
    -6.6 to 1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.85
    Confidence Interval (2-Sided) 95%
    -16.6 to -9.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -14.87
    Confidence Interval (2-Sided) 95%
    -18.6 to -11.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1808
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.56
    Confidence Interval (2-Sided) 95%
    -6.3 to 1.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.31
    Confidence Interval (2-Sided) 95%
    -16.1 to -8.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -14.70
    Confidence Interval (2-Sided) 95%
    -18.5 to -10.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2077
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.44
    Confidence Interval (2-Sided) 95%
    -6.2 to 1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.26
    Confidence Interval (2-Sided) 95%
    -16.1 to -8.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    30. Secondary Outcome
    Title Percentage of Participants Achieving an Acceptable State on the Patient Acceptable Symptom State (PASS) at Baseline and Week 36
    Description PASS was a 1 question assessment of how rheumatoid arthritis has affected the participant in the last 2 days (If you were to remain in the next few months as you were during the last 2 days, would this be acceptable or unacceptable to you?).
    Time Frame Baseline, Week 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 824
    Baseline
    44.90
    5.4%
    Week 36
    86.80
    10.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    31. Secondary Outcome
    Title Percentage of Participants Achieving an Acceptable State on the PASS at Week 36 and Weeks 64 and 88
    Description PASS was a 1 question assessment of how rheumatoid arthritis has affected the participant in the last 2 days (If you were to remain in the next few months as you were during the last 2 days, would this be acceptable or unacceptable to you?).
    Time Frame Weeks 36, 64 and 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 188 178 185
    Week 36
    93.5
    11.2%
    89.9
    NaN
    93.9
    NaN
    Week 64
    90.0
    10.8%
    88.7
    NaN
    65.8
    NaN
    Week 88
    91.3
    10.9%
    84.7
    NaN
    70.1
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8974
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.10
    Confidence Interval (2-Sided) 95%
    0.5 to 2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1105
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.67
    Confidence Interval (2-Sided) 95%
    0.8 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1900
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.67
    Confidence Interval (2-Sided) 95%
    0.3 to 1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.18
    Confidence Interval (2-Sided) 95%
    2.3 to 7.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4032
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.24
    Confidence Interval (2-Sided) 95%
    0.6 to 2.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.23
    Confidence Interval (2-Sided) 95%
    2.4 to 7.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.92
    Confidence Interval (2-Sided) 95%
    2.1 to 7.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0272
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.90
    Confidence Interval (2-Sided) 95%
    1.0 to 3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.34
    Confidence Interval (2-Sided) 95%
    1.4 to 4.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    32. Secondary Outcome
    Title Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good or Moderate Response at Weeks 4, 8, 12, 20, 28 and 36
    Description EULAR Response Criteria: Good response was defined as >1.2 units improvement in DAS28 from Baseline and DAS28 attained up to Week 88 of <=3.2 units. Non responders were participants with improvement of <0.6 units or participants with improvement of 0.6 to 1.2 units and DAS28 attained up to Week 88 of > 5.1 units. Remaining participants were defined as having a moderate response. Scores of good and moderate were considered to have therapeutic response.
    Time Frame Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 823
    Week 4
    61.95
    7.4%
    Week 8
    75.37
    9%
    Week 12
    82.03
    9.8%
    Week 20
    86.63
    10.4%
    Week 28
    87.24
    10.5%
    Week 36
    87.97
    10.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 4
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 8
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 12
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 20
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    33. Secondary Outcome
    Title Percentage of Participants Achieving EULAR Good or Moderate Response at Week 36, 40, 48, 56, 64, 72, 80 and 88
    Description EULAR Response Criteria: Good response was defined as >1.2 units improvement in DAS28 from Baseline and DAS28 attained up to Week 88 of <=3.2 units. Non responders were participants with improvement of <0.6 units or participants with improvement of 0.6 to 1.2 units and DAS28 attained up to Week 88 of > 5.1 units. Remaining participants were defined as having a moderate response. Scores of good and moderate were considered to have therapeutic response.
    Time Frame Week 36, 40, 48, 56, 64, 72, 80 and 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 198 199 191
    Week 36
    99.0
    11.9%
    99.0
    NaN
    97.5
    NaN
    Week 40
    93.8
    11.2%
    95.4
    NaN
    76.1
    NaN
    Week 48
    91.0
    10.9%
    92.0
    NaN
    64.0
    NaN
    Week 56
    90.0
    10.8%
    91.5
    NaN
    64.5
    NaN
    Week 64
    92.0
    11%
    91.5
    NaN
    62.4
    NaN
    Week 72
    93.0
    11.2%
    89.1
    NaN
    61.4
    NaN
    Week 80
    92.0
    11%
    89.1
    NaN
    60.4
    NaN
    Week 88
    90.5
    10.9%
    88.1
    NaN
    61.9
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1718
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.29
    Confidence Interval (2-Sided) 95%
    0.5 to 10.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8303
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.17
    Confidence Interval (2-Sided) 95%
    0.2 to 7.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2130
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.27
    Confidence Interval (2-Sided) 95%
    0.5 to 10.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.10
    Confidence Interval (2-Sided) 95%
    2.1 to 8.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4337
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.81
    Confidence Interval (2-Sided) 95%
    0.3 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.14
    Confidence Interval (2-Sided) 95%
    2.5 to 10.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.61
    Confidence Interval (2-Sided) 95%
    3.0 to 10.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8973
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.88
    Confidence Interval (2-Sided) 95%
    0.4 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.33
    Confidence Interval (2-Sided) 95%
    2.8 to 10.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.40
    Confidence Interval (2-Sided) 95%
    2.4 to 8.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5708
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.81
    Confidence Interval (2-Sided) 95%
    0.4 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.58
    Confidence Interval (2-Sided) 95%
    3.0 to 10.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 6.29
    Confidence Interval (2-Sided) 95%
    3.3 to 12.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8842
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.91
    Confidence Interval (2-Sided) 95%
    0.4 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.92
    Confidence Interval (2-Sided) 95%
    3.2 to 10.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 7.39
    Confidence Interval (2-Sided) 95%
    3.8 to 14.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1608
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.42
    Confidence Interval (2-Sided) 95%
    0.6 to 3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.92
    Confidence Interval (2-Sided) 95%
    2.9 to 8.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 6.44
    Confidence Interval (2-Sided) 95%
    3.4 to 12.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2825
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.21
    Confidence Interval (2-Sided) 95%
    0.6 to 2.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.59
    Confidence Interval (2-Sided) 95%
    2.7 to 7.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.81
    Confidence Interval (2-Sided) 95%
    2.7 to 8.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4471
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.06
    Confidence Interval (2-Sided) 95%
    0.5 to 2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.19
    Confidence Interval (2-Sided) 95%
    2.5 to 7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    34. Secondary Outcome
    Title Percentage of Participants With an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 4, 8, 12, 20, 28 and 36
    Description ACR20 response, ≥ 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and = at least 20% improvement in at least 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant (ESR).
    Time Frame Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 824
    Week 4
    38.62
    4.6%
    Week 8
    53.14
    6.4%
    Week 12
    61.29
    7.3%
    Week 20
    66.87
    8%
    Week 28
    70.75
    8.5%
    Week 36
    72.82
    8.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 4
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 8
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 12
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 20
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    35. Secondary Outcome
    Title Percentage of Participants With an ACR20 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
    Description ACR20 response: ≥ 20% improvement in tender joint count; ≥20% improvement in swollen joint count; and = at least 20% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).
    Time Frame Weeks 36, 40, 48, 56, 64, 72, 80 and 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF; N=number of participants with evaluable data
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 200 201 197
    Week 36
    86.5
    10.4%
    85.1
    NaN
    88.3
    NaN
    Week 40
    76.9
    9.2%
    77.7
    NaN
    61.2
    NaN
    Week 48
    77.0
    9.2%
    76.1
    NaN
    50.3
    NaN
    Week 56
    75.0
    9%
    74.6
    NaN
    50.3
    NaN
    Week 64
    76.5
    9.2%
    74.1
    NaN
    48.7
    NaN
    Week 72
    78.0
    9.4%
    74.6
    NaN
    47.2
    NaN
    Week 80
    79.5
    9.5%
    77.6
    NaN
    46.7
    NaN
    Week 88
    75.5
    9.1%
    74.6
    NaN
    48.7
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6006
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.83
    Confidence Interval (2-Sided) 95%
    0.4 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4967
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.10
    Confidence Interval (2-Sided) 95%
    0.6 to 2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3648
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.76
    Confidence Interval (2-Sided) 95%
    0.4 to 1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0024
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.98
    Confidence Interval (2-Sided) 95%
    1.2 to 3.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8308
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.92
    Confidence Interval () 95%
    0.6 to 1.
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0008
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.13
    Confidence Interval (2-Sided) 95%
    1.3 to 3.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.25
    Confidence Interval (2-Sided) 95%
    2.0 to 5.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7374
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.09
    Confidence Interval (2-Sided) 95%
    0.7 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.04
    Confidence Interval (2-Sided) 95%
    1.9 to 4.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.03
    Confidence Interval (2-Sided) 95%
    1.9 to 4.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9599
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.05
    Confidence Interval (2-Sided) 95%
    0.6 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.98
    Confidence Interval (2-Sided) 95%
    1.9 to 4.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.59
    Confidence Interval (2-Sided) 95%
    2.3 to 5.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4509
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.23
    Confidence Interval (2-Sided) 95%
    0.8 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.96
    Confidence Interval (2-Sided) 95%
    1.9 to 4.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.28
    Confidence Interval (2-Sided) 95%
    2.6 to 7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3037
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.20
    Confidence Interval (2-Sided) 95%
    0.7 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.27
    Confidence Interval (2-Sided) 95%
    2.1 to 5.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.41
    Confidence Interval (2-Sided) 95%
    2.7 to 7.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6076
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.13
    Confidence Interval (2-Sided) 95%
    0.7 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.80
    Confidence Interval (2-Sided) 95%
    2.4 to 6.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.85
    Confidence Interval (2-Sided) 95%
    1.8 to 4.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7837
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.95
    Confidence Interval (2-Sided) 95%
    0.6 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.03
    Confidence Interval (2-Sided) 95%
    2.0 to 4.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    36. Secondary Outcome
    Title Percentage of Participants With an ACR50 Response at Weeks 4, 8, 12, 20, 28 and 36
    Description ACR50 response: ≥ 50% improvement in tender joint count; = ≥50% improvement in swollen joint count; and = at least 50% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).
    Time Frame Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 824
    Week 4
    11.25
    1.3%
    Week 8
    22.88
    2.7%
    Week 12
    31.99
    3.8%
    Week 20
    41.99
    5%
    Week 28
    51.33
    6.2%
    Week 36
    59.83
    7.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 4
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 8
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 12
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 20
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    37. Secondary Outcome
    Title Percentage of Participants With an ACR50 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
    Description ACR50 response: ≥ 50% improvement in tender joint count; = ≥50% improvement in swollen joint count; and = at least 50% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).
    Time Frame Weeks 36, 40, 48, 56, 64, 72, 80 and 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 200 201 197
    Week 36
    76.5
    9.2%
    70.6
    NaN
    74.1
    NaN
    Week 40
    60.5
    7.3%
    57.9
    NaN
    41.0
    NaN
    Week 48
    58.0
    7%
    59.2
    NaN
    33.5
    NaN
    Week 56
    62.0
    7.4%
    56.2
    NaN
    28.9
    NaN
    Week 64
    59.0
    7.1%
    55.7
    NaN
    27.9
    NaN
    Week 72
    63.0
    7.6%
    53.7
    NaN
    26.9
    NaN
    Week 80
    62.5
    7.5%
    58.7
    NaN
    27.4
    NaN
    Week 88
    62.5
    7.5%
    57.2
    NaN
    25.9
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5263
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.20
    Confidence Interval (2-Sided) 95%
    0.7 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1055
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.41
    Confidence Interval (2-Sided) 95%
    0.9 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4348
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.85
    Confidence Interval (2-Sided) 95%
    0.5 to 1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0003
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.16
    Confidence Interval (2-Sided) 95%
    1.4 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5511
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.11
    Confidence Interval (2-Sided) 95%
    0.7 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0013
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.92
    Confidence Interval (2-Sided) 95%
    1.3 to 2.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.79
    Confidence Interval (2-Sided) 95%
    1.8 to 4.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9225
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.97
    Confidence Interval (2-Sided) 95%
    0.6 to 1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.95
    Confidence Interval (2-Sided) 95%
    1.9 to 4.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.20
    Confidence Interval (2-Sided) 95%
    2.7 to 6.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2454
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.32
    Confidence Interval (2-Sided) 95%
    0.9 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.15
    Confidence Interval (2-Sided) 95%
    2.0 to 4.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.83
    Confidence Interval (2-Sided) 95%
    2.4 to 6.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4919
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.22
    Confidence Interval (2-Sided) 95%
    0.8 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.16
    Confidence Interval (2-Sided) 95%
    2.0 to 4.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.80
    Confidence Interval (2-Sided) 95%
    3.0 to 7.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0658
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.47
    Confidence Interval (2-Sided) 95%
    1.0 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.03
    Confidence Interval (2-Sided) 95%
    2.0 to 4.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.32
    Confidence Interval (2-Sided) 95%
    2.7 to 6.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4014
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.25
    Confidence Interval (2-Sided) 95%
    0.8 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.54
    Confidence Interval (2-Sided) 95%
    2.3 to 5.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.53
    Confidence Interval (2-Sided) 95%
    2.9 to 7.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2824
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.23
    Confidence Interval (2-Sided) 95%
    0.8 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.83
    Confidence Interval (2-Sided) 95%
    2.5 to 5.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    38. Secondary Outcome
    Title Percentage of Participants With an ACR70 Response at Weeks 4, 8, 12, 20, 28 and 36
    Description ACR70 response: ≥ 70% improvement in tender joint count; = ≥70% improvement in swollen joint count; and = at least 70% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).
    Time Frame Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 824
    Week 4
    2.81
    0.3%
    Week 8
    6.77
    0.8%
    Week 12
    10.26
    1.2%
    Week 20
    16.75
    2%
    Week 28
    22.45
    2.7%
    Week 36
    27.79
    3.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 4
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 8
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 12
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 20
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    39. Secondary Outcome
    Title Percentage of Participants With an ACR70 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
    Description ACR70 response: ≥ 70% improvement in tender joint count; = ≥70% improvement in swollen joint count; and = at least 70% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and C-Reactive Protein CRP.
    Time Frame Weeks 36, 40, 48, 56, 64, 72, 80 and 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; N=number of participants with evaluable data; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 200 201 197
    Week 36
    42.0
    5%
    33.3
    NaN
    33.0
    NaN
    Week 40
    28.7
    3.4%
    27.9
    NaN
    17.6
    NaN
    Week 48
    28.0
    3.4%
    30.8
    NaN
    9.6
    NaN
    Week 56
    31.0
    3.7%
    31.3
    NaN
    10.2
    NaN
    Week 64
    33.0
    4%
    28.9
    NaN
    10.2
    NaN
    Week 72
    32.0
    3.8%
    31.3
    NaN
    10.7
    NaN
    Week 80
    34.0
    4.1%
    30.3
    NaN
    10.7
    NaN
    Week 88
    35.5
    4.3%
    31.3
    NaN
    11.2
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0575
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.49
    Confidence Interval (2-Sided) 95%
    1.0 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0630
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.48
    Confidence Interval (2-Sided) 95%
    1.0 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9160
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.02
    Confidence Interval (2-Sided) 95%
    0.7 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0147
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.76
    Confidence Interval (2-Sided) 95%
    1.0 to 3.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8675
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.02
    Confidence Interval (2-Sided) 95%
    0.6 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0174
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.77
    Confidence Interval (2-Sided) 95%
    1.1 to 3.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.24
    Confidence Interval (2-Sided) 95%
    1.9 to 5.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4941
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.85
    Confidence Interval (2-Sided) 95%
    0.5 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.01
    Confidence Interval (2-Sided) 95%
    2.3 to 7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.40
    Confidence Interval (2-Sided) 95%
    2.0 to 5.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8185
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.95
    Confidence Interval (2-Sided) 95%
    0.6 to 1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.66
    Confidence Interval (2-Sided) 95%
    2.1 to 6.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.78
    Confidence Interval (2-Sided) 95%
    2.2 to 6.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4254
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.17
    Confidence Interval (2-Sided) 95%
    0.7 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.38
    Confidence Interval (2-Sided) 95%
    1.9 to 5.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.26
    Confidence Interval (2-Sided) 95%
    1.8 to 5.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8766
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.06
    Confidence Interval (2-Sided) 95%
    0.7 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.67
    Confidence Interval (2-Sided) 95%
    2.1 to 6.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.53
    Confidence Interval (2-Sided) 95%
    2.0 to 6.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3535
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.21
    Confidence Interval (2-Sided) 95%
    0.8 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.44
    Confidence Interval (2-Sided) 95%
    1.9 to 6.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.45
    Confidence Interval (2-Sided) 95%
    2.0 to 6.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3231
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.25
    Confidence Interval (2-Sided) 95%
    0.8 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.23
    Confidence Interval (2-Sided) 95%
    1.9 to 5.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    40. Secondary Outcome
    Title Percentage of Participants With an ACR90 Response at Weeks 4, 8, 12, 20, 28 and 36
    Description ACR90 response: ≥ 90% improvement in tender joint count; = ≥90% improvement in swollen joint count; and = at least 90% improvement in 3 of the following 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).
    Time Frame Weeks 4, 8, 12, 20, 28 and 36

    Outcome Measure Data

    Analysis Population Description
    P1 mITT; LOCF
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
    Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
    Measure Participants 824
    Week 4
    1.02
    0.1%
    Week 8
    1.23
    0.1%
    Week 12
    1.83
    0.2%
    Week 20
    4.13
    0.5%
    Week 28
    6.31
    0.8%
    Week 36
    8.25
    1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 4
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 8
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 12
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 20
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    41. Secondary Outcome
    Title Percentage of Participants With an ACR90 Response at Weeks 36, 40, 48, 56, 64, 72, 80 and 88
    Description ACR90 response: ≥ 90% improvement in tender joint count; = 90% improvement in swollen joint count; and = 90% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase reactant (ESR).
    Time Frame Weeks 36, 40, 48, 56, 64, 72, 80 and 88

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 200 201 197
    Week 36
    13.5
    1.6%
    14.4
    NaN
    5.6
    NaN
    Week 40
    10.3
    1.2%
    9.1
    NaN
    4.8
    NaN
    Week 48
    10.0
    1.2%
    9.5
    NaN
    2.5
    NaN
    Week 56
    9.5
    1.1%
    9.0
    NaN
    2.0
    NaN
    Week 64
    10.5
    1.3%
    11.9
    NaN
    2.5
    NaN
    Week 72
    12.0
    1.4%
    13.9
    NaN
    2.5
    NaN
    Week 80
    14.0
    1.7%
    12.9
    NaN
    3.0
    NaN
    Week 88
    17.0
    2%
    14.4
    NaN
    3.6
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0089
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.14
    Confidence Interval (2-Sided) 95%
    0.9 to 5.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6932
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.87
    Confidence Interval (2-Sided) 95%
    0.5 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0019
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.76
    Confidence Interval (2-Sided) 95%
    1.2 to 6.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0797
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.53
    Confidence Interval (2-Sided) 95%
    0.6 to 3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8103
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.90
    Confidence Interval (2-Sided) 95%
    0.4 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0903
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.87
    Confidence Interval (2-Sided) 95%
    0.8 to 4.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0035
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.02
    Confidence Interval (2-Sided) 95%
    1.2 to 7.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9770
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.01
    Confidence Interval (2-Sided) 95%
    0.5 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0036
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.29
    Confidence Interval (2-Sided) 95%
    1.3 to 8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0038
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.80
    Confidence Interval (2-Sided) 95%
    1.0 to 7.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9055
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.98
    Confidence Interval (2-Sided) 95%
    0.5 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 56
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0020
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.36
    Confidence Interval (2-Sided) 95%
    1.2 to 9.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0020
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.35
    Confidence Interval (2-Sided) 95%
    1.3 to 8.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5763
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.87
    Confidence Interval (2-Sided) 95%
    0.4 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 64
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.93
    Confidence Interval (2-Sided) 95%
    1.5 to 10.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.21
    Confidence Interval (2-Sided) 95%
    1.2 to 8.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4828
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.83
    Confidence Interval (2-Sided) 95%
    0.4 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 72
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.52
    Confidence Interval (2-Sided) 95%
    1.4 to 9.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.28
    Confidence Interval (2-Sided) 95%
    1.4 to 7.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8553
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.03
    Confidence Interval (2-Sided) 95%
    0.6 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 80
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0003
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.56
    Confidence Interval (2-Sided) 95%
    1.5 to 8.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.53
    Confidence Interval (2-Sided) 95%
    1.6 to 7.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5025
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.12
    Confidence Interval (2-Sided) 95%
    0.6 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
    Comments Week 88
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0001
    Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.62
    Confidence Interval (2-Sided) 95%
    1.6 to 8.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    42. Secondary Outcome
    Title DAS28 at Week 36
    Description The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (>5.1=high disease activity; <=3.2=low disease activity; <2.6=remission); a continuous variable which is a composite of 4 variables (the number of tender joints out of 28, the number of swollen joints out of 28 joints, ESR mm/hour and PGA of disease activity measured on a VAS of 100 mm).
    Time Frame Week 36

    Outcome Measure Data

    Analysis Population Description
    P2 mITT; LOCF
    Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
    Measure Participants 201 201 197
    Mean (Standard Error) [units on a scale]
    1.99
    (0.04)
    2.06
    (0.04)
    2.07
    (0.04)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participants and as nonserious in another participants, or one participants may have experienced both a serious and nonserious event during the study.
    Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1 Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Arm/Group Description Participants received etanercept (ETN) 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks. Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) less than or equal to (≤) 3.2 at Week 36 and an average DAS28 less than or equal to (≤) 3.2 from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ 3.2 from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ 3.2 from Week 12 visit through Week 36.
    All Cause Mortality
    Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1 Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1 Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 38/834 (4.6%) 13/202 (6.4%) 7/202 (3.5%) 15/200 (7.5%)
    Blood and lymphatic system disorders
    Anaemia 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Cardiac disorders
    Atrial fibrillation 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Myocardial infarction 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Acute myocardial infarction 0/834 (0%) 0/202 (0%) 1/202 (0.5%) 0/200 (0%)
    Angina pectoris 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Eye disorders
    Refraction disorder 0/834 (0%) 0/202 (0%) 1/202 (0.5%) 0/200 (0%)
    Gastrointestinal disorders
    Gastrointestinal haemorrhage 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Rectal haemorrhage 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Gastric ulcer 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Gastritis 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Polyp colorectal 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Umbilical hernia 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    General disorders
    Pyrexia 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Oedema peripheral 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Immune system disorders
    Sarcoidosis 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Infections and infestations
    Arthritis bacterial 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Bronchopneumonia 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Cellulitis 2/834 (0.2%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Cystitis 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    H1N1 influenza 1/834 (0.1%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Pneumonia 5/834 (0.6%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Pyelonephritis acute 2/834 (0.2%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Tooth abscess 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Bronchitis 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Gastroenteritis 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Sepsis 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 1/200 (0.5%)
    Upper respiratory tract infection 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Urinary tract infection 0/834 (0%) 0/202 (0%) 0/202 (0%) 2/200 (1%)
    Injury, poisoning and procedural complications
    Accidental overdose 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Facial bones fracture 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Foreign body 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Joint sprain 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Tibia fracture 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Upper limb fracture 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Overdose 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Musculoskeletal and connective tissue disorders
    Bursitis 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Chondropathy 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Osteonecrosis 1/834 (0.1%) 0/202 (0%) 1/202 (0.5%) 0/200 (0%)
    Arthralgia 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Intervertebral disc protrusion 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Muscular weakness 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Rheumatoid arthritis 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 2/834 (0.2%) 0/202 (0%) 1/202 (0.5%) 0/200 (0%)
    Cervicitis human papilloma virus 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Colon cancer 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Uterine leiomyoma 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Bladder cancer 0/834 (0%) 0/202 (0%) 1/202 (0.5%) 0/200 (0%)
    Bladder neoplasm 0/834 (0%) 0/202 (0%) 1/202 (0.5%) 0/200 (0%)
    Malignant melanoma 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 1/200 (0.5%)
    Malignant melanoma in situ 0/834 (0%) 0/202 (0%) 1/202 (0.5%) 0/200 (0%)
    Ovarian adenoma 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Prostate cancer 0/834 (0%) 0/202 (0%) 1/202 (0.5%) 0/200 (0%)
    Squamous cell carcinoma of skin 0/834 (0%) 0/202 (0%) 1/202 (0.5%) 0/200 (0%)
    Thyroid cancer 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Nervous system disorders
    Carotid artery stenosis 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Headache 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Transient ischaemic attack 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Cerebral infarction 0/834 (0%) 0/202 (0%) 1/202 (0.5%) 0/200 (0%)
    Cerebrovascular accident 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Convulsion 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Pregnancy, puerperium and perinatal conditions
    Pregnancy 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Psychiatric disorders 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Depression 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Psychiatric disorders
    Depression 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Renal and urinary disorders
    Calculus urinary 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Renal failure acute 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Haematuria 0/834 (0%) 0/202 (0%) 1/202 (0.5%) 0/200 (0%)
    Urinary bladder polyp 0/834 (0%) 0/202 (0%) 1/202 (0.5%) 0/200 (0%)
    Reproductive system and breast disorders
    Endometrial hyperplasia 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Chronic obstructive pulmonary disease 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Pneumonitis 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Pulmonary embolism 0/834 (0%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Skin and subcutaneous tissue disorders
    Skin ulcer 1/834 (0.1%) 1/202 (0.5%) 0/202 (0%) 0/200 (0%)
    Vascular disorders
    Deep vein thrombosis 1/834 (0.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)
    Thrombophlebitis 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Venous thrombosis 0/834 (0%) 0/202 (0%) 0/202 (0%) 1/200 (0.5%)
    Other (Not Including Serious) Adverse Events
    Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1 Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 94/834 (11.3%) 32/202 (15.8%) 23/202 (11.4%) 25/200 (12.5%)
    Infections and infestations
    Nasopharyngitis 48/834 (5.8%) 18/202 (8.9%) 10/202 (5%) 10/200 (5%)
    Bronchitis 0/834 (0%) 12/202 (5.9%) 11/202 (5.4%) 6/200 (3%)
    Pharyngitis 0/834 (0%) 3/202 (1.5%) 5/202 (2.5%) 11/200 (5.5%)
    Nervous system disorders
    Headache 51/834 (6.1%) 0/202 (0%) 0/202 (0%) 0/200 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT00565409
    Other Study ID Numbers:
    • 0881A1-4423
    • B1801003
    First Posted:
    Nov 30, 2007
    Last Update Posted:
    Aug 10, 2015
    Last Verified:
    Aug 1, 2015