Open-Label Extension Treatment With Etanercept (TNFR:Fc) for Participating Patients in Etanercept (TNFR:Fc) Clinical Trial 016.0012

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00356590
• Collaborator: Immunex Corporation (Industry)
• Enrollment: 468
• Arm: 1
• Duration (Months): 124

Study Details

Study Description

Brief Summary

This is an open label, multicenter study for extended treatment of patients who have participated in the Immunex clinical study 016.0012. The primary objective of this study is to evaluate the long term safety of etanercept (TNFR:Fc) in patients with early stage rheumatoid arthritis.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Biological: Etanercept	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 468 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label Extension Treatment With Etanercept (TNFR:Fc) for Participating Patients in Etanercept (TNFR:Fc) Clinical Trial 016.0012
• Study Start Date: Dec 1, 1998
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: 1	Biological: Etanercept; Etanercept (TNFR:Fc) will be administered 50 mg per week as two 25 mg subcutaneous injections at separate sites, given either on the same day or 3 or 4 days apart.

Outcome Measures

Primary Outcome Measures

1. Total Exposure to Etanercept With Gaps [Up to 8 years]

   Total participant exposure to etanercept (Enbrel) with gaps, calculated as the sum of the times on treatment for all participants. Gaps of up to 14 days from the last treatment in a previous Etanercept study were ignored in calculating time on treatment.

2. Total Exposure-Adjusted Rate of Malignancies [Up to 8 years]

   Exposure-adjusted rate of malignancies, excluding nonmelanoma skin cancers, occurring on study within 30 days of the last dose of etanercept

3. Total Exposure-Adjusted Rate of Deaths [Up to 8 years]

   Rate of deaths within 30 days of the last dose of etanercept, adjusted for total exposure to etanercept

4. Total Exposure Adjusted Rate of Serious Infectious Events [Up to 8 years]

   Exposure-adjusted rate of serious infectious events (associated with hospitalization or IV antibiotics) occurring on study within 30 days of the last dose of etanercept

5. Total Exposure Adjusted Rate of Lymphomas [Up to 8 years]

   Rate of lymphomas occurring on study within 30 days of the last dose of etanercept, adjusted for total exposure to etanercept

6. Malignancy [Up to 8 years]

   Occurrence of one or more malignancies within the participant on study within 30 days of the last dose of etanercept

7. Lymphoma [Up to 8 years]

   Occurrence of one or more lymphomas on study within 30 days of the last dose of etanercept

8. Serious Infectious Event [Up to 8 years]

   Occurrence of one or more serious infectious events within the participant on study within 30 days of the last dose of study medication

9. Total Exposure Adjusted Rate of Serious Adverse Events [Up to 8 years]

   Rate of serious adverse events adjusted to total exposure to etanercept (events / exposure * 100)

10. Death [Up to 8 years]

    Death of the participant on study up to 30 days after the last dose of etanercept

Secondary Outcome Measures

1. ACR20 Response at Month 3 [Baseline and month 3]

   American College of Rheumatology (ACR) 20, defined as a 20% improvement in both tender and swollen joints (78 joints) and a 20% improvement in 3 of 5 items (physician and patient global assessments, patient pain assessment, patient self-assessed disability, and acute-phase C-reactive protein or erythrocyte sedimentation rate)

2. Dosing Period [Up to 8 years]

   Duration of etanercept dosing

3. ACR20 Response at Month 12 [Baseline and month 12]

   American College of Rheumatology (ACR) 20, defined as a 20% improvement in both tender and swollen joints (78 joints) and a 20% improvement in 3 of 5 items (including physician and patient global assessments), in adults

4. ACR50 Response at Month 12 [Baseline and month 12]

   American College of Rheumatology (ACR) 50, defined as a 50% improvement in both tender and swollen joints (78 joints) and a 50% improvement in 3 of 5 items (including physician and patient global assessments), in adults

5. ACR70 Response at Month 12 [Baseline and month 12]

   American College of Rheumatology (ACR) 70, defined as a 70% improvement in both tender and swollen joints (78 joints) and a 70% improvement in 3 of 5 items (including physician and patient global assessments), in adults

6. Standardized Incidence Rate for All SEER Cancers [Up to 8 years]

   Standardized incidence rate for all cancers tracked by the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) system, calculated as the ratio of the observed to expected age- and sex-adjusted incidence rates (per person-year) of cancer. Expected rates were based on 1998-2002 SEER data.

7. Percent Improvement in Physician Global Assessment of Disease Status From Baseline to Month 12 [Baseline and month 12]

   Percent improvement in the Physician Global Assessment of disease status from baseline to month 12, assessed using a 0 - 10 Likert scale, where 0 = asymptomatic and 10 = severe symptoms

8. Percent Improvement in Participant Global Assessment of Disease Status From Baseline to Month 12 [Baseline and Month 12]

   Percent improvement in the Participant Global Assessment of disease status from baseline to month 12, assessed using a 0 - 10 Likert scale, where 0 = asymptomatic and 10 = severe symptoms

9. Percent Improvement in Participant Pain Visual Analog Scale From Baseline to Month 12 [Baseline and month 12]

   Percent improvement in the Participant Pain Visual Analog Scale (VAS) from baseline to month 12, using a 10 cm scale ranging from "no pain" (0 cm) to "severe pain" (10 cm).

10. Percent Improvement in Tender Joint Count From Baseline to Month 12 [Baseline and month 12]

    Percent improvement in tender joint count (based on up to 71 joints) from baseline to month 12. Tender joints were assessed clinically, and the number of such joints was counted at each time point.

11. Percent Improvement in Swollen Joint Count From Baseline to Month 12 [Baseline and month 12]

    Percent improvement in swollen joint count (based on up to 68 joints) from baseline to month 12.

12. Percent Improvement in HAQ DI From Baseline to Month 12 [Baseline and month 12]

    Percent improvement in the Health Assessment Questionnaire Disability Index (HAQ DI) from baseline to month 12.

13. Percent Improvement in the Physical Component Summary Score for SF-36 From Baseline to Month 12 [Baseline and month 12]

    Percent improvement in the Physical Component Summary Score for the Short Form 36 Health Survey (SF-36) from baseline to month 12. This score has a range of 0 to 100, with higher scores indicating better health.

14. Percent Improvement in Mental Component Summary Score of SF-36 From Baseline to Month 12 [Baseline and month 12]

    Percent improvement in the Mental Component Summary Score of the Short Form 36 Health Survey (SF-36) from baseline to month 12. This score has a range of 0 to 100, with higher scores indicating better health.

15. Percent Improvement in C-Reactive Protein From Baseline to Month 12 [Baseline and month 12]

    Percent improvement in C-reactive protein from baseline to month 12

16. Percent Improvement in Duration of Morning Stiffness From Baseline to Month 12 [Baseline and month 12]

    Percent improvement in the duration of morning stiffness from baseline to month 12

17. Change From Baseline to Year 2 in Total Sharp Score [Baseline, Year 2]

    Change from baseline to year 2 in Total Sharp Score. This score has a range of 0 to 398, where 0 = no change and higher scores represent a worsening of joint erosions and joint space narrowing.

18. Change From Baseline to Year 2 in Sharp Score Erosion Subscale [Baseline, Year 2]

    Change from baseline to year 2 in the joint erosion subscale of the Total Sharp Score. This subscale has a range of 0 to 230, where 0 = no change and higher values represent a worsening in joint erosions.

19. Change From Baseline to Year 2 in Sharp Score Joint Space Narrowing Subscale [Baseline, Year 2]

    Change from baseline to year 2 in the joint space narrowing subscale of the Total Sharp Score. This subscale has a range of 0 to 168, where 0 = no change and higher values represent a worsening of joint space narrowing.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria: - Previous enrollment in Immunex protocol 016.0012.

• No clinically significant adverse events thought to be due to etanercept (TNFR:Fc) during previous treatment.

• Negative serum pregnancy test not more than 14 days before the first dose of study drug in females of childbearing potential.

• No more than one NSAID at a dose not greater than the maximum recommended dose and stable for at least two weeks prior to administration of etanercept (TNFR:Fc).

Exclusion Criteria:

• Previous receipt of etanercept (TNFR:Fc) (p55), antibody to TNF, anti-CD4 antibody, or diphtheria IL-2 fusion protein.

• Receipt of investigational drugs or biologics (other than etanercept (TNFR:Fc)) within interval between study drug in 016.0012 and this study.

• Receipt of DMARDs (e.g., hydroxychloroquine, oral or injectable gold, azathioprine, cyclosporin, D-penicillamine, sulfasalazine, minocycline, or leflunomide) other than MTX within two weeks prior to the first dose of etanercept (TNFR:Fc) in this study.

• Receipt of cyclophosphamide within 1 month prior to the first dose of etanercept (TNFR:Fc) in this study.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen
• Immunex Corporation

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00356590
• Other Study ID Numbers: 20021623; 16.0023
• First Posted: Jul 26, 2006
• Last Update Posted: May 14, 2013
• Last Verified: May 1, 2013

• Keywords provided by Amgen: Rheumatoid Arthritis; Etanercept; Long-term Safety; Enbrel
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Etanercept

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 3 March 1999 through 17 Mar 2000

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Period Title: Overall Study
STARTED	468
COMPLETED	194
NOT COMPLETED	274

Baseline Characteristics

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Overall Participants	468
Age (Year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Year]	51.38 (12.38)
Sex: Female, Male (Count of Participants)
Female	351 75%
Male	117 25%
Race/Ethnicity, Customized (Participant) [Number]
Hispanic or Latino	25
White or Caucasian	407
Other	4
American Indian or Alaska Native	4
Asian	5
Black or African American	23
Physician Global Assessment of Disease Status (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	5.32 (2.30)
Participant Global Assessment of Disease Status (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	5.51 (2.27)
Participant Pain Visual Analog Scale (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	5.01 (2.62)
Tender Joint Count (Joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Joints]	25.81 (16.71)
Swollen Joint Count (Joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Joints]	20.30 (12.60)
Health Assessment Questionnaire Disability Index (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	1.30 (0.67)
Physical Component Summary Score from SF-36 (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	30.42 (9.69)
Mental Component Summary Score from SF-36 (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	48.28 (11.52)
C-Reactive Protein (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	3.28 (4.90)
Duration of Morning Stiffness (Minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Minutes]	182.24 (286.63)

Outcome Measures

1. Primary Outcome

Title	Total Exposure to Etanercept With Gaps
Description	Total participant exposure to etanercept (Enbrel) with gaps, calculated as the sum of the times on treatment for all participants. Gaps of up to 14 days from the last treatment in a previous Etanercept study were ignored in calculating time on treatment.
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	468
Number [Participant-years]	2882.50

2. Secondary Outcome

Title	ACR20 Response at Month 3
Description	American College of Rheumatology (ACR) 20, defined as a 20% improvement in both tender and swollen joints (78 joints) and a 20% improvement in 3 of 5 items (physician and patient global assessments, patient pain assessment, patient self-assessed disability, and acute-phase C-reactive protein or erythrocyte sedimentation rate)
Time Frame	Baseline and month 3

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data at month 3

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	450
Number [Participants]	276 59%

3. Primary Outcome

Title	Total Exposure-Adjusted Rate of Malignancies
Description	Exposure-adjusted rate of malignancies, excluding nonmelanoma skin cancers, occurring on study within 30 days of the last dose of etanercept
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	468
Number [Malignancies per 100 participant-years]	1.32

4. Primary Outcome

Title	Total Exposure-Adjusted Rate of Deaths
Description	Rate of deaths within 30 days of the last dose of etanercept, adjusted for total exposure to etanercept
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	468
Number [Deaths per 100 participant-years]	0.35

5. Primary Outcome

Title	Total Exposure Adjusted Rate of Serious Infectious Events
Description	Exposure-adjusted rate of serious infectious events (associated with hospitalization or IV antibiotics) occurring on study within 30 days of the last dose of etanercept
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	468
Number [Events per 100 participant-years]	2.88

6. Primary Outcome

Title	Total Exposure Adjusted Rate of Lymphomas
Description	Rate of lymphomas occurring on study within 30 days of the last dose of etanercept, adjusted for total exposure to etanercept
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	468
Number [Lymphomas per 100 participant-years]	0.24

7. Primary Outcome

Title	Malignancy
Description	Occurrence of one or more malignancies within the participant on study within 30 days of the last dose of etanercept
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	468
Number [Participants]	31 6.6%

8. Primary Outcome

Title	Lymphoma
Description	Occurrence of one or more lymphomas on study within 30 days of the last dose of etanercept
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	468
Number [Participants]	6 1.3%

9. Primary Outcome

Title	Serious Infectious Event
Description	Occurrence of one or more serious infectious events within the participant on study within 30 days of the last dose of study medication
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	468
Number [Participants]	51 10.9%

10. Primary Outcome

Title	Total Exposure Adjusted Rate of Serious Adverse Events
Description	Rate of serious adverse events adjusted to total exposure to etanercept (events / exposure * 100)
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	468
Number [Events per 100 patient-years]	13.84

11. Secondary Outcome

Title	Dosing Period
Description	Duration of etanercept dosing
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of etanercept

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	468
Mean (Standard Deviation) [Days]	2249.6 (1180.00)

12. Secondary Outcome

Title	ACR20 Response at Month 12
Description	American College of Rheumatology (ACR) 20, defined as a 20% improvement in both tender and swollen joints (78 joints) and a 20% improvement in 3 of 5 items (including physician and patient global assessments), in adults
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data at month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	424
Number [Participants]	262 56%

13. Secondary Outcome

Title	ACR50 Response at Month 12
Description	American College of Rheumatology (ACR) 50, defined as a 50% improvement in both tender and swollen joints (78 joints) and a 50% improvement in 3 of 5 items (including physician and patient global assessments), in adults
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data at month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	424
Number [Participants]	192 41%

14. Secondary Outcome

Title	ACR70 Response at Month 12
Description	American College of Rheumatology (ACR) 70, defined as a 70% improvement in both tender and swollen joints (78 joints) and a 70% improvement in 3 of 5 items (including physician and patient global assessments), in adults
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data at month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	424
Number [Participants]	110 23.5%

15. Secondary Outcome

Title	Standardized Incidence Rate for All SEER Cancers
Description	Standardized incidence rate for all cancers tracked by the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) system, calculated as the ratio of the observed to expected age- and sex-adjusted incidence rates (per person-year) of cancer. Expected rates were based on 1998-2002 SEER data.
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of etanercept

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	468
Mean (95% Confidence Interval) [Standardized incidence rate]	0.99

16. Secondary Outcome

Title	Percent Improvement in Physician Global Assessment of Disease Status From Baseline to Month 12
Description	Percent improvement in the Physician Global Assessment of disease status from baseline to month 12, assessed using a 0 - 10 Likert scale, where 0 = asymptomatic and 10 = severe symptoms
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	417
Mean (Standard Deviation) [Percent change]	50.07 (58.07)

17. Secondary Outcome

Title	Percent Improvement in Participant Global Assessment of Disease Status From Baseline to Month 12
Description	Percent improvement in the Participant Global Assessment of disease status from baseline to month 12, assessed using a 0 - 10 Likert scale, where 0 = asymptomatic and 10 = severe symptoms
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	419
Mean (Standard Deviation) [Percent change]	35.46 (60.62)

18. Secondary Outcome

Title	Percent Improvement in Participant Pain Visual Analog Scale From Baseline to Month 12
Description	Percent improvement in the Participant Pain Visual Analog Scale (VAS) from baseline to month 12, using a 10 cm scale ranging from "no pain" (0 cm) to "severe pain" (10 cm).
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	422
Mean (Standard Deviation) [Percent change]	30.64 (103.25)

19. Secondary Outcome

Title	Percent Improvement in Tender Joint Count From Baseline to Month 12
Description	Percent improvement in tender joint count (based on up to 71 joints) from baseline to month 12. Tender joints were assessed clinically, and the number of such joints was counted at each time point.
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	417
Mean (Standard Deviation) [Percent change]	49.70 (147.16)

20. Secondary Outcome

Title	Percent Improvement in Swollen Joint Count From Baseline to Month 12
Description	Percent improvement in swollen joint count (based on up to 68 joints) from baseline to month 12.
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	412
Mean (Standard Deviation) [Percent change]	52.04 (87.97)

21. Secondary Outcome

Title	Percent Improvement in HAQ DI From Baseline to Month 12
Description	Percent improvement in the Health Assessment Questionnaire Disability Index (HAQ DI) from baseline to month 12.
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	420
Mean (Standard Deviation) [Percent change]	40.91 (66.09)

22. Secondary Outcome

Title	Percent Improvement in the Physical Component Summary Score for SF-36 From Baseline to Month 12
Description	Percent improvement in the Physical Component Summary Score for the Short Form 36 Health Survey (SF-36) from baseline to month 12. This score has a range of 0 to 100, with higher scores indicating better health.
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	422
Mean (Standard Deviation) [Percent change]	-39.65 (55.43)

23. Secondary Outcome

Title	Percent Improvement in Mental Component Summary Score of SF-36 From Baseline to Month 12
Description	Percent improvement in the Mental Component Summary Score of the Short Form 36 Health Survey (SF-36) from baseline to month 12. This score has a range of 0 to 100, with higher scores indicating better health.
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	422
Mean (Standard Deviation) [Percent change]	-12.31 (31.48)

24. Secondary Outcome

Title	Percent Improvement in C-Reactive Protein From Baseline to Month 12
Description	Percent improvement in C-reactive protein from baseline to month 12
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	423
Mean (Standard Deviation) [Percent change]	31.57 (132.83)

25. Secondary Outcome

Title	Percent Improvement in Duration of Morning Stiffness From Baseline to Month 12
Description	Percent improvement in the duration of morning stiffness from baseline to month 12
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and month 12

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	411
Mean (Standard Deviation) [Percent change]	44.08 (156.20)

26. Primary Outcome

Title	Death
Description	Death of the participant on study up to 30 days after the last dose of etanercept
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	468
Number [Participants]	10 2.1%

27. Secondary Outcome

Title	Change From Baseline to Year 2 in Total Sharp Score
Description	Change from baseline to year 2 in Total Sharp Score. This score has a range of 0 to 398, where 0 = no change and higher scores represent a worsening of joint erosions and joint space narrowing.
Time Frame	Baseline, Year 2

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and year 2

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	274
Mean (Full Range) [Units on a scale]	1.17

28. Secondary Outcome

Title	Change From Baseline to Year 2 in Sharp Score Erosion Subscale
Description	Change from baseline to year 2 in the joint erosion subscale of the Total Sharp Score. This subscale has a range of 0 to 230, where 0 = no change and higher values represent a worsening in joint erosions.
Time Frame	Baseline, Year 2

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and year 2

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	274
Mean (Full Range) [Units on a scale]	0.54

29. Secondary Outcome

Title	Change From Baseline to Year 2 in Sharp Score Joint Space Narrowing Subscale
Description	Change from baseline to year 2 in the joint space narrowing subscale of the Total Sharp Score. This subscale has a range of 0 to 168, where 0 = no change and higher values represent a worsening of joint space narrowing.
Time Frame	Baseline, Year 2

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of etanercept and had available data for this outcome measure at baseline and year 2

Arm/Group Title	Etanercept (Enbrel)
Arm/Group Description	Etanercept 50 mg subcutaneous dose weekly
Measure Participants	274
Mean (Full Range) [Units on a scale]	0.64

Adverse Events

Time Frame	Up to 9.57 years
Adverse Event Reporting Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Arm/Group Title	Enbrel
Arm/Group Description
All Cause Mortality
	Enbrel
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Enbrel
	Affected / at Risk (%)	# Events
Total	169/468 (36.1%)
Blood and lymphatic system disorders
Anaemia	1/468 (0.2%)
Iron deficiency anaemia	1/468 (0.2%)
Cardiac disorders
Acute myocardial infarction	4/468 (0.9%)
Angina pectoris	2/468 (0.4%)
Angina unstable	4/468 (0.9%)
Arrhythmia	3/468 (0.6%)
Atrial fibrillation	7/468 (1.5%)
Atrial flutter	1/468 (0.2%)
Bradyarrhythmia	1/468 (0.2%)
Cardiac arrest	2/468 (0.4%)
Cardiac failure congestive	5/468 (1.1%)
Coronary artery disease	6/468 (1.3%)
Coronary artery occlusion	2/468 (0.4%)
Coronary artery stenosis	1/468 (0.2%)
Myocardial infarction	8/468 (1.7%)
Palpitations	1/468 (0.2%)
Pericarditis	1/468 (0.2%)
Supraventricular tachycardia	1/468 (0.2%)
Ventricular tachycardia	1/468 (0.2%)
Congenital, familial and genetic disorders
Cleft palate	1/468 (0.2%)
Endocrine disorders
Myxoedema	1/468 (0.2%)
Gastrointestinal disorders
Abdominal pain	3/468 (0.6%)
Abdominal pain lower	1/468 (0.2%)
Constipation	1/468 (0.2%)
Diarrhoea	1/468 (0.2%)
Diverticulum	1/468 (0.2%)
Gastric ulcer haemorrhage	1/468 (0.2%)
Gastrointestinal haemorrhage	1/468 (0.2%)
Ileus	2/468 (0.4%)
Intestinal ischaemia	1/468 (0.2%)
Nausea	2/468 (0.4%)
Pancreatitis	2/468 (0.4%)
Peptic ulcer	1/468 (0.2%)
Retroperitoneal haemorrhage	1/468 (0.2%)
Small intestinal obstruction	1/468 (0.2%)
Vomiting	1/468 (0.2%)
General disorders
Adverse drug reaction	1/468 (0.2%)
Asthenia	1/468 (0.2%)
Chest pain	9/468 (1.9%)
Condition aggravated	11/468 (2.4%)
Death	1/468 (0.2%)
Impaired healing	1/468 (0.2%)
Non-cardiac chest pain	2/468 (0.4%)
Hepatobiliary disorders
Cholecystitis	5/468 (1.1%)
Cholelithiasis	2/468 (0.4%)
Immune system disorders
Anaphylactic shock	1/468 (0.2%)
Infections and infestations
Abdominal abscess	1/468 (0.2%)
Abdominal infection	1/468 (0.2%)
Abscess	1/468 (0.2%)
Anorectal infection	1/468 (0.2%)
Appendicitis perforated	1/468 (0.2%)
Arthritis bacterial	1/468 (0.2%)
Bacteraemia	2/468 (0.4%)
Bronchitis	6/468 (1.3%)
Bronchitis bacterial	1/468 (0.2%)
Bursitis infective	1/468 (0.2%)
Cellulitis	6/468 (1.3%)
Cholecystitis infective	1/468 (0.2%)
Cystitis	1/468 (0.2%)
Diarrhoea infectious	1/468 (0.2%)
Diverticulitis	1/468 (0.2%)
Empyema	1/468 (0.2%)
Gastroenteritis	3/468 (0.6%)
Haemophilus sepsis	1/468 (0.2%)
Infection	2/468 (0.4%)
Localised infection	1/468 (0.2%)
Lung infection pseudomonal	2/468 (0.4%)
Orchitis	1/468 (0.2%)
Pelvic abscess	1/468 (0.2%)
Perirectal abscess	1/468 (0.2%)
Peritonsillar abscess	1/468 (0.2%)
Pneumonia	15/468 (3.2%)
Pneumonia escherichia	1/468 (0.2%)
Pneumonia klebsiella	1/468 (0.2%)
Pneumonia staphylococcal	1/468 (0.2%)
Post procedural infection	1/468 (0.2%)
Pseudomembranous colitis	1/468 (0.2%)
Pseudomonas infection	1/468 (0.2%)
Pyelonephritis	3/468 (0.6%)
Pyelonephritis acute	1/468 (0.2%)
Sepsis	1/468 (0.2%)
Staphylococcal infection	2/468 (0.4%)
Staphylococcal sepsis	1/468 (0.2%)
Streptococcal infection	1/468 (0.2%)
Urinary tract infection	3/468 (0.6%)
Urosepsis	3/468 (0.6%)
Viral infection	1/468 (0.2%)
Wound infection	1/468 (0.2%)
Injury, poisoning and procedural complications
Ankle fracture	1/468 (0.2%)
Fall	1/468 (0.2%)
Femoral neck fracture	1/468 (0.2%)
Fibula fracture	1/468 (0.2%)
Fracture displacement	1/468 (0.2%)
Hand fracture	1/468 (0.2%)
Hip fracture	4/468 (0.9%)
Humerus fracture	2/468 (0.4%)
Lower limb fracture	1/468 (0.2%)
Muscle strain	1/468 (0.2%)
Pelvic fracture	1/468 (0.2%)
Procedural pain	1/468 (0.2%)
Pseudomeningocele	1/468 (0.2%)
Spinal compression fracture	2/468 (0.4%)
Tibia fracture	2/468 (0.4%)
Ulna fracture	2/468 (0.4%)
Wrist fracture	1/468 (0.2%)
Investigations
Biopsy prostate	1/468 (0.2%)
Colonoscopy	1/468 (0.2%)
Metabolism and nutrition disorders
Dehydration	2/468 (0.4%)
Diabetes mellitus	1/468 (0.2%)
Hypoglycaemia	2/468 (0.4%)
Hypokalaemia	1/468 (0.2%)
Hyponatraemia	1/468 (0.2%)
Obesity	1/468 (0.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/468 (0.6%)
Arthritis	1/468 (0.2%)
Arthropathy	3/468 (0.6%)
Back pain	1/468 (0.2%)
Bone disorder	1/468 (0.2%)
Cervical spinal stenosis	1/468 (0.2%)
Intervertebral disc protrusion	1/468 (0.2%)
Lumbar spinal stenosis	2/468 (0.4%)
Musculoskeletal pain	2/468 (0.4%)
Osteoarthritis	8/468 (1.7%)
Rheumatoid arthritis	6/468 (1.3%)
Rotator cuff syndrome	1/468 (0.2%)
Spinal column stenosis	1/468 (0.2%)
Spinal osteoarthritis	1/468 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	1/468 (0.2%)
B-cell lymphoma	2/468 (0.4%)
B-cell small lymphocytic lymphoma	1/468 (0.2%)
Basal cell carcinoma	2/468 (0.4%)
Benign colonic neoplasm	1/468 (0.2%)
Benign neoplasm of thyroid gland	1/468 (0.2%)
Breast cancer	3/468 (0.6%)
Breast cancer in situ	1/468 (0.2%)
Breast cancer metastatic	1/468 (0.2%)
Chronic lymphocytic leukaemia	1/468 (0.2%)
Colon cancer	2/468 (0.4%)
Lung neoplasm	1/468 (0.2%)
Lung neoplasm malignant	2/468 (0.4%)
Lung squamous cell carcinoma stage II	1/468 (0.2%)
Lymphocytic lymphoma	1/468 (0.2%)
Malignant melanoma	4/468 (0.9%)
Metastases to spine	1/468 (0.2%)
Metastatic malignant melanoma	1/468 (0.2%)
Neuroendocrine carcinoma	1/468 (0.2%)
Non-Hodgkin's lymphoma	1/468 (0.2%)
Non-Hodgkin's lymphoma stage IV	1/468 (0.2%)
Non-small cell lung cancer metastatic	1/468 (0.2%)
Prostate cancer	5/468 (1.1%)
Renal cancer	1/468 (0.2%)
Squamous cell carcinoma	1/468 (0.2%)
Squamous cell carcinoma of skin	1/468 (0.2%)
T-cell chronic lymphocytic leukaemia	1/468 (0.2%)
Thyroid cancer	1/468 (0.2%)
Uterine leiomyoma	2/468 (0.4%)
Nervous system disorders
Cerebral haemorrhage	1/468 (0.2%)
Cerebrovascular accident	5/468 (1.1%)
Headache	2/468 (0.4%)
Hypoaesthesia	1/468 (0.2%)
Intracranial aneurysm	2/468 (0.4%)
Multiple sclerosis	1/468 (0.2%)
Myelopathy	1/468 (0.2%)
Presyncope	1/468 (0.2%)
Ruptured cerebral aneurysm	2/468 (0.4%)
Syncope	4/468 (0.9%)
Transient ischaemic attack	1/468 (0.2%)
Psychiatric disorders
Adjustment disorder	1/468 (0.2%)
Confusional state	1/468 (0.2%)
Conversion disorder	1/468 (0.2%)
Depression	1/468 (0.2%)
Mental status changes	1/468 (0.2%)
Suicidal ideation	3/468 (0.6%)
Renal and urinary disorders
IgA nephropathy	1/468 (0.2%)
Renal failure	1/468 (0.2%)
Renal mass	1/468 (0.2%)
Urinary retention	1/468 (0.2%)
Reproductive system and breast disorders
Endometriosis	1/468 (0.2%)
Prostatic disorder	1/468 (0.2%)
Uterine haemorrhage	1/468 (0.2%)
Respiratory, thoracic and mediastinal disorders
Asthma	4/468 (0.9%)
Chronic obstructive pulmonary disease	3/468 (0.6%)
Dyspnoea	1/468 (0.2%)
Dyspnoea exertional	1/468 (0.2%)
Hypoxia	1/468 (0.2%)
Lung infiltration	1/468 (0.2%)
Pleural effusion	3/468 (0.6%)
Pleuritic pain	1/468 (0.2%)
Pneumothorax	2/468 (0.4%)
Pulmonary embolism	3/468 (0.6%)
Pulmonary mass	1/468 (0.2%)
Respiratory distress	1/468 (0.2%)
Skin and subcutaneous tissue disorders
Stasis dermatitis	1/468 (0.2%)
Surgical and medical procedures
Cholecystectomy	1/468 (0.2%)
Cystopexy	1/468 (0.2%)
Incisional hernia repair	1/468 (0.2%)
Knee arthroplasty	4/468 (0.9%)
Shoulder arthroplasty	1/468 (0.2%)
Spinal laminectomy	1/468 (0.2%)
Surgery	1/468 (0.2%)
Vascular disorders
Aortic aneurysm	1/468 (0.2%)
Arterial thrombosis	1/468 (0.2%)
Deep vein thrombosis	3/468 (0.6%)
Haemorrhage	1/468 (0.2%)
Hypertension	1/468 (0.2%)
Hypotension	1/468 (0.2%)
Lymphoedema	1/468 (0.2%)
Peripheral ischaemia	1/468 (0.2%)
Thrombosis	3/468 (0.6%)
Other (Not Including Serious) Adverse Events
	Enbrel
	Affected / at Risk (%)	# Events
Total	320/468 (68.4%)
Gastrointestinal disorders
Dyspepsia	28/468 (6%)
Nausea	26/468 (5.6%)
General disorders
Fatigue	26/468 (5.6%)
Injection site erythema	51/468 (10.9%)
Injection site pruritus	26/468 (5.6%)
Injection site swelling	25/468 (5.3%)
Infections and infestations
Bronchitis	49/468 (10.5%)
Cystitis	27/468 (5.8%)
Influenza	42/468 (9%)
Sinusitis	91/468 (19.4%)
Upper respiratory tract infection	106/468 (22.6%)
Nervous system disorders
Headache	46/468 (9.8%)
Psychiatric disorders
Depression	27/468 (5.8%)
Skin and subcutaneous tissue disorders
Rash	36/468 (7.7%)
Vascular disorders
Hypertension	24/468 (5.1%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multi-center studies, the investigator agrees not to publish any results before the first multi-center publication.