DOSERA: Study Comparing The Effect On Disease Activity When Reducing Or Discontinuing Etanercept In Subjects With RA

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00858780
• Collaborator: (none)
• Enrollment: 91
• Locations: 16
• Arms: 3
• Duration (Months): 41
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study involves Rheumatoid Arthritis patients in regular clinical setting who are already on etanercept treatment and are in remission or in a low disease activity (LDA) state, and is intended to identify parameters that can serve as guidance in clinical settings. This study will consider the clinical and radiographic course in subjects when etanercept treatment is tapered or discontinued, and analyze the subjects' experience of disease worsening and the predictive values of clinical parameters, serum biomarkers and imaging on the clinical and radiographic course in different treatment groups. The effect of re-treatment with etanercept at treatment failure will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Etanercept; Drug: Etanercept; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 91 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Dose Reduction or Discontinuation of Etanercept in Methotrexate-Treated Rheumatoid Arthritis Subjects Who Have Achieved a Stable Low Disease Activity-state (DOSERA)
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 50mg once weekly + methotrexate	Drug: Etanercept; 50 mg etanercept once weekly + methotrexate
Active Comparator: 2 25mg once weekly + methotrexate	Drug: Etanercept; 25mg etanercept once weekly + methotrexate
Placebo Comparator: 3 once weekly + methotrexate	Drug: Placebo; Placebo comparator once weekly + methotrexate

Outcome Measures

Primary Outcome Measures

1. Percentage of Participant Who Were Non-Failures [Week 48]

   A participant was considered as non-failure if the calculated DAS28 <=3.2 at all visits or if the calculated DAS28 >3.2, the increase of calculated DAS28 from randomization (Week 0): was <0.6 at all visit or was >=0.6 but <1.2 on no more than 1 consecutive visit. Percentage of participants who were non-failures calculated based on DAS28 and disease progression as determined by investigator or participant.

Secondary Outcome Measures

1. Time to Treatment Failure (TTF) [Randomization (Week 0) up to date of failure, withdrawal due to disease progression or last evaluation visit (Week 48)]

   TTF (in weeks): (date of failure minus date of randomization) divided by 7. Date of failure was ordinary visit date or extra visit date in case of failure (extra visit was within 2 weeks from the date a participant experienced significant disease progression between visits and wanted to withdraw from Period 2), or date of withdrawal due to disease progression. Participants who did not have a treatment failure were censored at their last evaluation visit. Participants who withdrew from the study prematurely and did not have a treatment failure were censored on the date of their withdrawal.

2. Percentage of Participants With Remission or Low Disease Activity (LDA) [Baseline (Week -8), Week -4, Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48]

   Participants who had DAS28 less than or equal to (<=) 3.2 were considered in remission or LDA state.

3. Percentage of Visits During Which Participants Were in Remission or Low Disease Activity State [Randomization (Week 0) up to Week 48]

   Participants who had DAS28 <=3.2 were considered in remission or LDA state. Percentage of visits during which a participant was in remission or LDA state was calculated as number of visits in which participant was in remission or LDA divided by total number of visits multiplied by 100.

4. Disease Activity Score Based on 28-Joint Count (DAS28) at Randomization [Randomization (Week 0)]

   DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <=3.2 implied low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity and less than (<) 2.6=remission.

5. Change From Randomization in Disease Activity Score Based on 28-Joint Count (DAS28) at Week 6, 12, 18, 24, 30, 36, 42, and 48 [Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48]

   DAS28 calculated from SJC and PJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <=3.2 = low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity and <2.6=remission.

6. Change From Randomization in Tender Joints Count (TJC) at Week 6, 12, 18, 24, 30, 36, 42, and 48 [Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48]

   Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. A negative value in change from randomization indicates an improvement.

7. Change From Randomization in Swollen Joints Count (SJC) at Week 6, 12, 18, 24, 30, 36, 42, and 48 [Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48]

   Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. A negative value in change from randomization indicates an improvement.

8. Change From Randomization in Physician Global Assessment (PGA) of Disease Activity at Week 6, 12, 18, 24, 30, 36, 42, and 48 [Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48]

   PGA of disease activity was measured on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), with 0 mm = no disease activity and 100 mm = extreme disease activity.

9. Change From Randomization in Participant Global Assessment (PtGA) of Disease Activity at Week 6, 12, 18, 24, 30, 36, 42, and 48 [Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48]

   Participants assessed the overall activity of their rheumatoid arthritis (RA) on a 0 to 100 mm VAS, where 0 mm = no disease activity and 100 mm = extreme disease activity.

10. Participant General Health Visual Analog Scale (VAS) at Randomization [Randomization (Week 0)]

    Participants answered "in general how would you rate your health over the last 2-3 weeks?" Participants responded by using a 0 to 100 mm VAS, where 0 mm = very well and 100 mm = extremely bad.

11. Change From Randomization in Participant General Health Visual Analog Scale (VAS) at Week 6, 12, 18, 24, 30, 36, 42, and 48 [Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48]

    Participants answered "in general how would you rate your health over the last 2-3 weeks?" Participants responded by using a 0 to 100 mm VAS, where 0 mm = very well and 100 mm = extremely bad.

12. Participant Pain Visual Analog Scale (VAS) at Randomization [Randomization (Week 0)]

    Participants indicated the amount of pain experience during the last 2-3 days by marking a vertical line on 100 mm VAS. Intensity of pain range: 0 = no pain to 100 = pain as bad as it could be.

13. Change From Randomization in Participant Pain Visual Analog Scale (VAS) at Week 6, 12, 18, 24, 30, 36, 42, and 48 [Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48]

    Participants indicated the amount of pain experience during the last 2-3 days by marking a vertical line on 100 mm VAS. Intensity of pain range: 0 = no pain to 100 = pain as bad as it could be.

14. Change From Randomization in Morning Stiffness Duration at Week 6, 12, 18, 24, 30, 36, 42, and 48 [Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48]

    Duration of morning stiffness: Time elapsed when participant woke up in morning and was able to resume normal activities without stiffness in minutes. The duration of morning stiffness was determined by asking the following questions: 1) Over the last 2 days, when did you wake in the morning? 2) Over the last 2 days, when were you able to resume your normal activities without stiffness? Increase in stiffness duration from randomization represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

15. Change From Randomization in Erythrocyte Sedimentation Rate (ESR) at Week 6, 12, 18, 24, 30, 36, 42, and 48 [Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48]

    ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 millimeter per hour (mm/hour). A higher rate is consistent with inflammation.

16. Change From Randomization in C-Reactive Protein (CRP) Level at Week 6, 12, 18, 24, 30, 36, 42, and 48 [Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48]

    The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is <10 milligram per liter (mg/L). A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

17. Change From Randomization in Modified Total Sharp Score (mTSS) at Week 48 [Randomization (Week 0), Week 48]

    mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at randomization. An increase in mTSS from randomization represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

18. Magnetic Resonance Imaging (MRI) Findings at Randomization [Randomization (Week 0)]

    MRI of hand/wrist of dominant hand scored for signs of synovitis (S-score), bone edema(O-score), bone erosions (E-score) as per outcome measures in RA clinical trials (OMERACT). S-score:0(normal)-3(severe) for distal radioulnar,radiocarpal,intercarpal-carpometacarpal,second-fifth metacarpophalangeal joints, total score(TS)0-21, higher score(HS)=severe synovitis. O-score:0(no volume increment)-3(100% volume increment) in 23 hand/wrist joints, TS 0-69, HS=more edema. E-score:0(no volume occupied by erosion)-10(100% volume occupied by erosion) in 23 hand/wrist joints, TS 0-230, HS=more erosion.

19. Change From Randomization in Magnetic Resonance Imaging (MRI) Findings (S-Score) at Week 12 [Randomization (Week 0), Week 12]

    MRI of hand/wrist of dominant hand was scored for signs of synovitis (S-score), bone edema (O-score), and bone erosions (E-score) as per OMERACT. S-score: 0 (normal) to 3 (severe) for each of distal radioulnar, radiocarpal, intercarpal-carpometacarpal, second to fifth metacarpophalangeal joints; total score 0 to 21, higher score=severe synovitis.

20. Change From Randomization in Magnetic Resonance Imaging (MRI) Findings (O-Score, E-Score) at Week 12 [Randomization (Week 0), Week 12]

    MRI of hand/wrist of dominant hand was scored for signs of synovitis (S-score), bone edema (O-score), and bone erosions (E-score) as per OMERACT. O-score: 0 (no volume increment) to 3 (100% volume increment) in 23 hand/wrist joints; total score 0 to 69, higher scores=more edema. E-score: 0 (no volume occupied by erosion) to 10 (100% volume occupied by erosion) in 23 hand/wrist joints; total score 0 to 230, higher scores=more erosion.

21. Percentage of Participants in Treatment Failure for Each Potentially Predictor Variable at Randomization [Randomization (Week 0) up to Week 48]

    Percentage of participants who were treatment failure over 48 weeks as per potentially predictor variables (at randomization) are reported: number of swollen joints/tender joints, DAS28, PGA, PtGA, participant general health VAS, participant pain VAS, clinical disease activity index (CDAI), simplified disease activity index (SDAI), ESR (mm/hour), plasma CRP (mg/L), sensitive serum CRP (mg/L), anti- cyclic citrullinated peptide (anti CCP, units/mL), cartilage oligomeric matrix protein (COMP, units/liter), S-score, O-score, E-score, Joint space narrowing score, erosion score, and mTSS.

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Subject has a current DAS28 equal to or less than 3.2.

• Subject is currently receiving treatment with etanercept, either 25 mg twice weekly or 50 mg once weekly, for a minimum of 14 months at baseline

• Subject is currently receiving oral, sc or intramuscular methotrexate once weekly, 7.5 mg/week to 25 mg/week and at a stable dose for a minimum of 4 months at baseline.

Exclusion Criteria:

• Subject has earlier had an attempt of discontinuing etanercept for reasons of remission or low disease activity state.

• Subject has received any disease-modifying anti-rheumatic drug, other than methotrexate, within one month before baseline.

• Subject has had a dose of prednisone (or equivalent) >7.5 mg/day or has received intra-articular, intravenous, intramuscular, or subcutaneous corticosteroid within one month of baseline.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Glostrup		Denmark	DK-2600
2	Pfizer Investigational Site	Hellerup		Denmark	2900
3	Pfizer Investigational Site	Helsinki		Finland	FI-00029 HUS
4	Pfizer Investigational Site	Jyvaskyla		Finland	40620
5	Pfizer Investigational Site	Gyula		Hungary	5701
6	Pfizer Investigational Site	Szombathely		Hungary	9700
7	Pfizer Investigational Site	Veszprem		Hungary	8200
8	Pfizer Investigational Site	Reykjavik		Iceland	108
9	Pfizer Investigational Site	Bergen		Norway	5021
10	Pfizer Investigational Site	Lillehammer		Norway	2609
11	Pfizer Investigational Site	Oslo		Norway	0319
12	Pfizer Investigational Site	Lund		Sweden	221 85
13	Pfizer Investigational Site	Malmo		Sweden	SE-205 02
14	Pfizer Investigational Site	Stockholm		Sweden	14186
15	Pfizer Investigational Site	Stockholm		Sweden	17176
16	Pfizer Investigational Site	Uppsala		Sweden	751 85

Sponsors and Collaborators

• Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00858780
• Other Study ID Numbers: 0881K1-4500; B1801016
• First Posted: Mar 10, 2009
• Last Update Posted: Sep 11, 2013
• Last Verified: Aug 1, 2013

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Etanercept

Study Results

Participant Flow

Arm/Group Title	Etanercept 50 mg - Period 1	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2	Etanercept 50 mg - Period 3
Arm/Group Description	Etanercept 50 milligram (mg) subcutaneous (SC) injection once weekly along with methotrexate (MTX) 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or intramuscular (IM) injection, depending on the dose a participant was receiving at time of screening, for 8 weeks. Participants who maintained disease activity score based on 28-joints count (DAS28) less than or equal to (<=) 3.2 in Period 1 were randomized in Period 2.	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Participants, who showed treatment failure in Period 2, received etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to Week 48/early termination.
Period Title: Open-Label (OL) Run-In(Week-8 to Week 0)
STARTED	91	0	0	0	0
COMPLETED	73	0	0	0	0
NOT COMPLETED	18	0	0	0	0
Period Title: Open-Label (OL) Run-In(Week-8 to Week 0)
STARTED	0	23	27	23	0
COMPLETED	0	21	25	22	0
NOT COMPLETED	0	2	2	1	0
Period Title: Open-Label (OL) Run-In(Week-8 to Week 0)
STARTED	0	0	0	0	43
COMPLETED	0	0	0	0	41
NOT COMPLETED	0	0	0	0	2

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	Includes all participants who were enrolled in this study.
Overall Participants	91
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.14 (11.60)
Sex: Female, Male (Count of Participants)
Female	65 71.4%
Male	26 28.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participant Who Were Non-Failures
Description	A participant was considered as non-failure if the calculated DAS28 <=3.2 at all visits or if the calculated DAS28 >3.2, the increase of calculated DAS28 from randomization (Week 0): was <0.6 at all visit or was >=0.6 but <1.2 on no more than 1 consecutive visit. Percentage of participants who were non-failures calculated based on DAS28 and disease progression as determined by investigator or participant.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (m-ITT) analysis set included all randomized participants who received at least 1 dose of study medication after randomization and had at least 1 available evaluation after the first administration of study medication after randomization.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	23
Number [percentage of participants]	52.2 57.4%	44.4 NaN	13.0 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept 50 mg - Period 2, Placebo - Period 2
	Comments	Analysis was performed using a generalized estimating equations (GEE) model, using a logit link, a binomial distribution and an auto-regressive correlation structure, with treatment groups, visits, their interaction, and the stratification factor as factors in the model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	GEE Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.17
	Confidence Interval	(2-Sided) 95%; 1.72 to 29.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept 50 mg - Period 2, Etanercept 25 mg - Period 2
	Comments	Analysis was performed using a GEE model, using a logit link, a binomial distribution and an auto-regressive correlation structure, with treatment groups, visits, their interaction, and the stratification factor as factors in the model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.362
	Comments
	Method	GEE Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 95%; 0.54 to 5.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 25 mg - Period 2, Placebo - Period 2
	Comments	Analysis was performed using a GEE model, using a logit link, a binomial distribution and an auto-regressive correlation structure, with treatment groups, visits, their interaction, and the stratification factor as factors in the model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.044
	Comments
	Method	GEE Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.20
	Confidence Interval	(2-Sided) 95%; 1.04 to 16.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to Treatment Failure (TTF)
Description	TTF (in weeks): (date of failure minus date of randomization) divided by 7. Date of failure was ordinary visit date or extra visit date in case of failure (extra visit was within 2 weeks from the date a participant experienced significant disease progression between visits and wanted to withdraw from Period 2), or date of withdrawal due to disease progression. Participants who did not have a treatment failure were censored at their last evaluation visit. Participants who withdrew from the study prematurely and did not have a treatment failure were censored on the date of their withdrawal.
Time Frame	Randomization (Week 0) up to date of failure, withdrawal due to disease progression or last evaluation visit (Week 48)

Outcome Measure Data

Analysis Population Description

m-ITT analysis set.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	23
Median (95% Confidence Interval) [weeks]	48.0	36.1	6.1

3. Secondary Outcome

Title	Percentage of Participants With Remission or Low Disease Activity (LDA)
Description	Participants who had DAS28 less than or equal to (<=) 3.2 were considered in remission or LDA state.
Time Frame	Baseline (Week -8), Week -4, Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, 'n' signifies participants evaluable for each time-point for each treatment arm, respectively.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	23
Baseline (n= 19, 23, 19)	100 109.9%	100 NaN	100 NaN
Week -4 (n= 23, 26, 23)	100 109.9%	100 NaN	100 NaN
Randomization (n= 22, 27, 23)	100 109.9%	96.3 NaN	100 NaN
Week 6 (n= 21, 26, 15)	90.5 99.5%	80.8 NaN	60.0 NaN
Week 12 (n= 18, 21, 6)	94.4 103.7%	85.7 NaN	83.3 NaN
Week 18 (n= 16, 19, 3)	87.5 96.2%	89.5 NaN	100 NaN
Week 24 (n= 14, 16, 3)	100 109.9%	100 NaN	100 NaN
Week 30 (n= 14, 15, 3)	92.9 102.1%	100 NaN	66.7 NaN
Week 36 (n= 13, 14, 2)	100 109.9%	85.7 NaN	100 NaN
Week 42 (n= 12, 12, 2)	100 109.9%	100 NaN	100 NaN
Week 48 (n= 12, 12, 2)	83.3 91.5%	91.7 NaN	100 NaN

4. Secondary Outcome

Title	Percentage of Visits During Which Participants Were in Remission or Low Disease Activity State
Description	Participants who had DAS28 <=3.2 were considered in remission or LDA state. Percentage of visits during which a participant was in remission or LDA state was calculated as number of visits in which participant was in remission or LDA divided by total number of visits multiplied by 100.
Time Frame	Randomization (Week 0) up to Week 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	22	27	15
Mean (Standard Deviation) [percentage of visits]	82.7 (31.1)	74.8 (38.0)	55.3 (48.5)

5. Secondary Outcome

Title	Disease Activity Score Based on 28-Joint Count (DAS28) at Randomization
Description	DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <=3.2 implied low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity and less than (<) 2.6=remission.
Time Frame	Randomization (Week 0)

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	22	27	23
Mean (Standard Deviation) [units on a scale]	1.86 (0.62)	1.93 (0.85)	1.93 (0.71)

6. Secondary Outcome

Title	Change From Randomization in Disease Activity Score Based on 28-Joint Count (DAS28) at Week 6, 12, 18, 24, 30, 36, 42, and 48
Description	DAS28 calculated from SJC and PJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <=3.2 = low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity and <2.6=remission.
Time Frame	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	21	26	15
Change at Week 6	0.11 (0.24)	0.47 (0.25)	0.85 (0.36)
Change at Week 12	0.38 (0.25)	0.32 (0.26)	1.33 (0.53)
Change at Week 18	0.41 (0.25)	0.64 (0.27)	1.14 (0.69)
Change at Week 24	-0.00 (0.26)	0.66 (0.28)	1.02 (0.69)
Change at Week 30	0.24 (0.26)	0.74 (0.28)	1.12 (0.69)
Change at Week 36	0.18 (0.26)	1.00 (0.28)	0.45 (0.80)
Change at Week 42	0.14 (0.27)	0.45 (0.29)	1.02 (0.80)
Change at Week 48	0.46 (0.27)	0.92 (0.29)	1.17 (0.80)

7. Secondary Outcome

Title	Change From Randomization in Tender Joints Count (TJC) at Week 6, 12, 18, 24, 30, 36, 42, and 48
Description	Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. A negative value in change from randomization indicates an improvement.
Time Frame	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, 'n' signifies participants evaluable for each time point for each treatment arm, respectively.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	23
Randomization (n=23,27,23)	0.0	0.0	0.0
Change at Week 6 (n= 22, 26, 15)	0.0	0.0	1.0
Change at Week 12 (n= 18, 21, 6)	0.0	0.0	0.5
Change at Week 18 (n= 16, 19, 3)	0.0	0.0	0.0
Change at Week 24 (n= 14, 16, 3)	0.0	0.0	0.0
Change at Week 30 (n= 14, 15, 3)	0.0	0.0	0.0
Change at Week 36 (n= 13, 14, 2)	0.0	0.0	-0.5
Change at Week 42 (n= 12, 12, 2)	0.0	0.0	-0.5
Change at Week 48 (n= 12, 12, 2)	0.0	0.0	0.5

8. Secondary Outcome

Title	Change From Randomization in Swollen Joints Count (SJC) at Week 6, 12, 18, 24, 30, 36, 42, and 48
Description	Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. A negative value in change from randomization indicates an improvement.
Time Frame	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, 'n' signifies participants evaluable for each time point for each treatment arm, respectively.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	23
Randomization (n=23,27,23)	0.0	0.0	0.0
Change at Week 6 (n= 22, 26, 15)	0.0	0.0	0.0
Change at Week 12 (n= 18, 21, 6)	0.0	0.0	1.0
Change at Week 18 (n= 16, 19, 3)	0.0	0.0	0.0
Change at Week 24 (n= 14, 16, 3)	0.0	0.0	0.0
Change at Week 30 (n= 14, 15, 3)	0.0	0.0	0.0
Change at Week 36 (n= 13, 14, 2)	0.0	0.0	0.0
Change at Week 42 (n= 12, 12, 2)	0.0	0.0	0.0
Change at Week 48 (n= 12, 12, 2)	0.0	0.0	0.5

9. Secondary Outcome

Title	Change From Randomization in Physician Global Assessment (PGA) of Disease Activity at Week 6, 12, 18, 24, 30, 36, 42, and 48
Description	PGA of disease activity was measured on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), with 0 mm = no disease activity and 100 mm = extreme disease activity.
Time Frame	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this measure and 'n' signifies participants evaluable for each time point for each treatment arm, respectively.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	22
Randomization (n=23,27,22)	4.00	3.00	2.25
Change at Week 6 (n= 22, 26, 14)	1.50	0.25	4.00
Change at Week 12 (n= 18, 21, 6)	1.00	0.50	6.75
Change at Week 18 (n= 16, 19, 3)	2.50	4.00	10.00
Change at Week 24 (n= 14, 15, 3)	1.00	2.00	8.00
Change at Week 30 (n= 14, 15, 3)	1.00	0.00	5.00
Change at Week 36 (n= 13, 14, 2)	0.00	0.00	-6.50
Change at Week 42 (n= 12, 12, 2)	0.25	-1.00	-3.00
Change at Week 48 (n= 12, 12, 2)	0.25	-1.75	-1.50

10. Secondary Outcome

Title	Change From Randomization in Participant Global Assessment (PtGA) of Disease Activity at Week 6, 12, 18, 24, 30, 36, 42, and 48
Description	Participants assessed the overall activity of their rheumatoid arthritis (RA) on a 0 to 100 mm VAS, where 0 mm = no disease activity and 100 mm = extreme disease activity.
Time Frame	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, 'n' signifies participants evaluable for each time point for each treatment arm, respectively.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	23
Randomization (n=23,27,23)	8.00	12.00	13.00
Change at Week 6 (n= 22, 26, 15)	2.50	0.25	10.00
Change at Week 12 (n= 18, 21, 6)	-0.25	0.00	18.00
Change at Week 18 (n= 16, 19, 3)	0.00	-0.50	20.00
Change at Week 24 (n= 14, 16, 3)	0.00	0.50	4.00
Change at Week 30 (n= 14, 15, 3)	-1.00	0.50	-5.50
Change at Week 36 (n= 13, 14, 2)	0.00	0.50	-24.00
Change at Week 42 (n= 12, 12, 2)	-0.50	-0.25	-7.50
Change at Week 48 (n= 12, 12, 2)	1.50	-1.00	-7.00

11. Secondary Outcome

Title	Participant General Health Visual Analog Scale (VAS) at Randomization
Description	Participants answered "in general how would you rate your health over the last 2-3 weeks?" Participants responded by using a 0 to 100 mm VAS, where 0 mm = very well and 100 mm = extremely bad.
Time Frame	Randomization (Week 0)

Outcome Measure Data

Analysis Population Description

m-ITT analysis set.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	23
Mean (Standard Deviation) [mm]	14.43 (12.87)	15.11 (13.15)	18.52 (15.35)

12. Secondary Outcome

Title	Change From Randomization in Participant General Health Visual Analog Scale (VAS) at Week 6, 12, 18, 24, 30, 36, 42, and 48
Description	Participants answered "in general how would you rate your health over the last 2-3 weeks?" Participants responded by using a 0 to 100 mm VAS, where 0 mm = very well and 100 mm = extremely bad.
Time Frame	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	23
Change at Week 6	8.21 (4.74)	8.67 (4.70)	8.37 (6.59)
Change at Week 12	4.09 (5.03)	10.21 (4.86)	18.47 (10.06)
Change at Week 18	8.14 (5.16)	12.29 (4.93)	11.30 (13.70)
Change at Week 24	9.86 (5.42)	9.70 (5.09)	-0.15 (13.71)
Change at Week 30	9.09 (5.38)	13.84 (5.11)	6.88 (13.71)
Change at Week 36	9.18 (5.49)	17.49 (5.16)	-3.20 (16.31)
Change at Week 42	8.15 (5.62)	14.01 (5.26)	29.87 (16.32)
Change at Week 48	12.04 (5.63)	16.09 (5.26)	6.36 (16.33)

13. Secondary Outcome

Title	Participant Pain Visual Analog Scale (VAS) at Randomization
Description	Participants indicated the amount of pain experience during the last 2-3 days by marking a vertical line on 100 mm VAS. Intensity of pain range: 0 = no pain to 100 = pain as bad as it could be.
Time Frame	Randomization (Week 0)

Outcome Measure Data

Analysis Population Description

m-ITT analysis set.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	23
Mean (Standard Deviation) [mm]	15.59 (18.16)	12.96 (10.92)	13.37 (10.05)

14. Secondary Outcome

Title	Change From Randomization in Participant Pain Visual Analog Scale (VAS) at Week 6, 12, 18, 24, 30, 36, 42, and 48
Description	Participants indicated the amount of pain experience during the last 2-3 days by marking a vertical line on 100 mm VAS. Intensity of pain range: 0 = no pain to 100 = pain as bad as it could be.
Time Frame	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	23
Change at Week 6	1.90 (3.32)	5.67 (3.69)	22.70 (6.39)
Change at Week 12	-3.05 (3.56)	8.05 (3.84)	34.27 (9.43)
Change at Week 18	2.21 (3.61)	12.21 (3.90)	12.91 (12.40)
Change at Week 24	-1.18 (3.88)	7.46 (4.06)	11.32 (12.41)
Change at Week 30	3.20 (3.81)	7.13 (4.08)	15.97 (12.41)
Change at Week 36	2.05 (3.90)	13.00 (4.15)	1.46 (14.49)
Change at Week 42	1.06 (4.02)	12.84 (4.26)	7.13 (14.49)
Change at Week 48	1.32 (4.06)	9.13 (4.28)	6.47 (14.50)

15. Secondary Outcome

Title	Change From Randomization in Morning Stiffness Duration at Week 6, 12, 18, 24, 30, 36, 42, and 48
Description	Duration of morning stiffness: Time elapsed when participant woke up in morning and was able to resume normal activities without stiffness in minutes. The duration of morning stiffness was determined by asking the following questions: 1) Over the last 2 days, when did you wake in the morning? 2) Over the last 2 days, when were you able to resume your normal activities without stiffness? Increase in stiffness duration from randomization represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time Frame	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this measure and 'n' signifies participants evaluable for each time point for each treatment arm, respectively.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	26	23
Randomization (n=23,26,23)	10.0	0.5	5.0
Change at Week 6 (n= 22, 25, 15)	0.0	0.0	0.0
Change at Week 12 (n= 18, 20, 5)	0.0	0.0	1.0
Change at Week 18 (n= 16, 19, 3)	0.0	0.0	0.0
Change at Week 24 (n= 14, 16, 3)	0.0	0.0	0.0
Change at Week 30 (n= 14, 15, 3)	0.0	0.0	-5.0
Change at Week 36 (n= 13, 14, 2)	0.0	0.0	-2.5
Change at Week 42 (n= 12, 11, 2)	0.0	0.0	-2.5
Change at Week 48 (n= 12, 11, 2)	0.0	0.0	-5.0

16. Secondary Outcome

Title	Change From Randomization in Erythrocyte Sedimentation Rate (ESR) at Week 6, 12, 18, 24, 30, 36, 42, and 48
Description	ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 millimeter per hour (mm/hour). A higher rate is consistent with inflammation.
Time Frame	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this measure and 'n' signifies participants evaluable for each time point for each treatment arm, respectively.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	22	27	23
Randomization (n=22,27,23)	10.00	8.00	8.00
Change at Week 6 (n= 21, 26, 15)	0.00	0.00	2.00
Change at Week 12 (n= 17, 21, 6)	0.00	0.00	0.50
Change at Week 18 (n= 15, 19, 3)	1.00	1.00	2.00
Change at Week 24 (n= 14, 16, 3)	-1.00	0.00	1.00
Change at Week 30 (n= 14, 15, 3)	-1.50	0.00	1.00
Change at Week 36 (n= 13, 14, 2)	0.00	1.50	-2.50
Change at Week 42 (n= 12, 12, 2)	-1.50	0.00	-0.50
Change at Week 48 (n= 12, 12, 2)	2.00	1.00	-2.50

17. Secondary Outcome

Title	Change From Randomization in C-Reactive Protein (CRP) Level at Week 6, 12, 18, 24, 30, 36, 42, and 48
Description	The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is <10 milligram per liter (mg/L). A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
Time Frame	Randomization (Week 0), Week 6, 12, 18, 24, 30, 36, 42, 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, 'n' signifies participants evaluable for each time point for each treatment arm, respectively.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	23
Randomization (n=23,27,23)	2.00	3.00	1.60
Change at Week 6 (n= 22, 26, 15)	0.00	0.00	0.33
Change at Week 12 (n= 18, 20, 6)	0.00	0.00	0.00
Change at Week 18 (n= 16, 19, 3)	0.00	0.00	2.74
Change at Week 24 (n= 14, 16, 3)	0.00	0.00	1.00
Change at Week 30 (n= 14, 15, 3)	0.00	0.00	1.20
Change at Week 36 (n= 13, 14, 2)	0.00	0.00	0.94
Change at Week 42 (n= 12, 12, 2)	0.00	0.00	3.49
Change at Week 48 (n= 12, 12, 2)	0.00	0.00	-1.42

18. Secondary Outcome

Title	Change From Randomization in Modified Total Sharp Score (mTSS) at Week 48
Description	mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at randomization. An increase in mTSS from randomization represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time Frame	Randomization (Week 0), Week 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this measure and 'n' signifies participants evaluable for each time point for each treatment arm, respectively.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	19	22	17
Randomization (n=19, 22, 17)	19.50	54.25	23.00
Change at Week 48 (n= 9, 9, 1)	0.00	0.00	-1.00

19. Secondary Outcome

Title	Magnetic Resonance Imaging (MRI) Findings at Randomization
Description	MRI of hand/wrist of dominant hand scored for signs of synovitis (S-score), bone edema(O-score), bone erosions (E-score) as per outcome measures in RA clinical trials (OMERACT). S-score:0(normal)-3(severe) for distal radioulnar,radiocarpal,intercarpal-carpometacarpal,second-fifth metacarpophalangeal joints, total score(TS)0-21, higher score(HS)=severe synovitis. O-score:0(no volume increment)-3(100% volume increment) in 23 hand/wrist joints, TS 0-69, HS=more edema. E-score:0(no volume occupied by erosion)-10(100% volume occupied by erosion) in 23 hand/wrist joints, TS 0-230, HS=more erosion.
Time Frame	Randomization (Week 0)

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	18	21	15
S-Score	4.19 (3.13)	4.90 (3.26)	4.37 (4.43)
O-Score	1.50 (1.34)	3.14 (3.95)	3.63 (3.36)
E-Score	12.53 (18.47)	25.10 (28.23)	12.60 (10.80)

20. Secondary Outcome

Title	Change From Randomization in Magnetic Resonance Imaging (MRI) Findings (S-Score) at Week 12
Description	MRI of hand/wrist of dominant hand was scored for signs of synovitis (S-score), bone edema (O-score), and bone erosions (E-score) as per OMERACT. S-score: 0 (normal) to 3 (severe) for each of distal radioulnar, radiocarpal, intercarpal-carpometacarpal, second to fifth metacarpophalangeal joints; total score 0 to 21, higher score=severe synovitis.
Time Frame	Randomization (Week 0), Week 12

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	15	14	3
Least Squares Mean (Standard Error) [units on a scale]	-0.16 (0.56)	1.36 (0.68)	-0.29 (1.15)

21. Secondary Outcome

Title	Change From Randomization in Magnetic Resonance Imaging (MRI) Findings (O-Score, E-Score) at Week 12
Description	MRI of hand/wrist of dominant hand was scored for signs of synovitis (S-score), bone edema (O-score), and bone erosions (E-score) as per OMERACT. O-score: 0 (no volume increment) to 3 (100% volume increment) in 23 hand/wrist joints; total score 0 to 69, higher scores=more edema. E-score: 0 (no volume occupied by erosion) to 10 (100% volume occupied by erosion) in 23 hand/wrist joints; total score 0 to 230, higher scores=more erosion.
Time Frame	Randomization (Week 0), Week 12

Outcome Measure Data

Analysis Population Description

m-ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	15	14	3
Change at Week 12: O-Score	0.00	0.00	-3.00
Change at Week 12: E-Score	0.00	0.00	0.00

22. Secondary Outcome

Title	Percentage of Participants in Treatment Failure for Each Potentially Predictor Variable at Randomization
Description	Percentage of participants who were treatment failure over 48 weeks as per potentially predictor variables (at randomization) are reported: number of swollen joints/tender joints, DAS28, PGA, PtGA, participant general health VAS, participant pain VAS, clinical disease activity index (CDAI), simplified disease activity index (SDAI), ESR (mm/hour), plasma CRP (mg/L), sensitive serum CRP (mg/L), anti- cyclic citrullinated peptide (anti CCP, units/mL), cartilage oligomeric matrix protein (COMP, units/liter), S-score, O-score, E-score, Joint space narrowing score, erosion score, and mTSS.
Time Frame	Randomization (Week 0) up to Week 48

Outcome Measure Data

Analysis Population Description

m-ITT analysis set.

Arm/Group Title	Etanercept 50 mg - Period 2	Etanercept 25 mg - Period 2	Placebo - Period 2
Arm/Group Description	Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.	Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.	Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.
Measure Participants	23	27	23
Number of swollen joints = 0 (n= 18, 21, 19)	44.4 48.8%	57.1 NaN	84.2 NaN
Number of swollen joints >0 (n= 5, 6, 4)	60.0 65.9%	50.0 NaN	100 NaN
Number of tender joints = 0 (n= 20, 19, 15)	45.0 49.5%	47.4 NaN	86.7 NaN
Number of tender joints >0 to 1 (n= 2, 4, 6)	100 109.9%	75.0 NaN	83.3 NaN
Number of tender joints > 1 (n= 0, 4, 2)	0.0 0%	75.0 NaN	100 NaN
DAS28 <=2.6 (n= 20, 21, 18)	40.0 44%	47.6 NaN	83.3 NaN
DAS28 >2.6 to 3.2 (n= 2, 5, 5)	100 109.9%	80.0 NaN	100 NaN
DAS28 >3.2 to 5.1 (n= 0, 1, 0)	0.0 0%	100 NaN	0.0 NaN
PGA = 0 (n= 6, 4, 9)	50.0 54.9%	25.0 NaN	88.9 NaN
PGA >0 to 3 (n= 5, 10, 3)	60.0 65.9%	60.0 NaN	100 NaN
PGA >3 to 7 (n= 9, 5, 5)	33.3 36.6%	40.0 NaN	80.0 NaN
PGA >7 (n= 3, 8, 5)	66.7 73.3%	75.0 NaN	80.0 NaN
PtGA <= 2.5 (n= 6, 8, 5)	66.7 73.3%	37.5 NaN	100 NaN
PtGA >2.5 to 11 (n= 7, 5, 6)	28.6 31.4%	60.0 NaN	83.3 NaN
PtGA >11 to 21 (n= 4, 7, 7)	50.0 54.9%	57.1 NaN	85.7 NaN
PtGA >21 (n= 6, 7, 5)	50.0 54.9%	71.4 NaN	80.0 NaN
Participant general health VAS <=3 (n= 6, 7, 6)	50.0 54.9%	28.6 NaN	83.3 NaN
Participant general health VAS >3 to 14 (n= 9,8,4)	44.4 48.8%	62.5 NaN	100 NaN
Participant general health VAS>14 to 26.5(n=2,7,7)	100 109.9%	57.1 NaN	71.4 NaN
Participant general health VAS >26.5 (n= 6, 5, 6)	33.3 36.6%	80.0 NaN	100 NaN
Participant pain VAS <=3 (n= 7, 8, 5)	57.1 62.7%	37.5 NaN	100 NaN
Participant pain VAS >3 to 10 (n= 6, 5, 6)	33.3 36.6%	20.0 NaN	83.3 NaN
Participant pain VAS >10 to 22 (n=3, 7, 8)	33.3 36.6%	85.7 NaN	87.5 NaN
Participant pain VAS >22 (n= 7, 7, 4)	57.1 62.7%	71.4 NaN	75.0 NaN
CDAI <= 2.8 (n= 14, 13, 13)	50.0 54.9%	46.2 NaN	84.6 NaN
CDAI >2.8 to 10 (n= 9, 14, 9)	44.4 48.8%	64.3 NaN	88.9 NaN
SDAI<= 3.3 (n= 8, 7, 8)	50.0 54.9%	28.6 NaN	75.0 NaN
SDAI>3.3 to 11 (n= 13, 15, 12)	38.5 42.3%	60.0 NaN	100 NaN
SDAI>11 to 26 (n= 2, 4, 2)	100 109.9%	75.0 NaN	50.0 NaN
SDAI>26 (n= 0, 1, 0)	0.0 0%	100 NaN	0.0 NaN
ESR<= 5 (n= 6, 8, 10)	66.7 73.3%	12.5 NaN	80.0 NaN
ESR >5 to 10 (n= 7, 9, 6)	28.6 31.4%	66.7 NaN	100 NaN
ESR >10 to 12.5 (n= 0, 3, 2)	0.0 0%	100 NaN	100 NaN
ESR >12.5 (n= 6, 7, 5)	66.7 73.3%	71.4 NaN	80.0 NaN
Plasma CRP <= 1 (n= 8, 8, 8)	62.5 68.7%	37.5 NaN	75.0 NaN
Plasma CRP >1 to 2 (n= 5, 2, 7)	20.0 22%	50.0 NaN	100 NaN
Plasma CRP >2 to 5 (n= 6, 11, 3)	16.7 18.4%	54.5 NaN	100 NaN
Plasma CRP >5 (n= 4, 6, 5)	100 109.9%	83.3 NaN	80.0 NaN
Sensitive serum CRP <= 0.6 (n= 7, 5, 6)	57.1 62.7%	20.0 NaN	83.3 NaN
Sensitive serum CRP >0.6 to 1.2 (n= 5, 5, 7)	40.0 44%	80.0 NaN	85.7 NaN
Sensitive serum CRP >1.2 to 3.3 (n= 6, 7, 5)	33.3 36.6%	42.9 NaN	100 NaN
Sensitive serum CRP >3.3 (n= 4, 8, 5)	75.0 82.4%	75.0 NaN	80.0 NaN
Anti-CCP <= 31.7 (n= 5, 8, 5)	40.0 44%	37.5 NaN	100 NaN
Anti-CCP >31.7 to 346.8 (n= 8, 3, 6)	75.0 82.4%	100 NaN	83.3 NaN
Anti-CCP >346.8 to 710.8 (n= 5, 4, 9)	20.0 22%	50.0 NaN	77.8 NaN
Anti-CCP >710.8 (n= 4, 10, 3)	50.0 54.9%	60.0 NaN	100 NaN
COMP <= 7.6 (n= 7, 5, 6)	28.6 31.4%	20.0 NaN	66.7 NaN
COMP >7.6 to 9.6 (n= 5, 4, 8)	60.0 65.9%	50.0 NaN	100 NaN
COMP >9.6 to 12.3 (n= 5, 11, 2)	80.0 87.9%	63.6 NaN	100 NaN
COMP >12.3 (n= 5, 5, 7)	40.0 44%	80.0 NaN	85.7 NaN
S-score <= 1.5 (n= 5, 5, 5)	20.0 22%	40.0 NaN	80.0 NaN
S-score >1.5 to 3.8 (n= 5, 2, 5)	20.0 22%	50.0 NaN	60.0 NaN
S-score >3.8 to 7.5 (n= 5, 8, 1)	80.0 87.9%	37.5 NaN	100 NaN
S-score >7.5 (n= 3, 6, 4)	66.7 73.3%	50.0 NaN	100 NaN
O-score <= 0.5 (n= 6, 7, 4)	16.7 18.4%	42.9 NaN	50.0 NaN
O-score >0.5 to 1.5 (n= 4, 6, 2)	25.0 27.5%	50.0 NaN	100 NaN
O-score >1.5 to 3.5 (n= 7, 0, 3)	71.4 78.5%	0.0 NaN	100 NaN
O-score >3.5 (n= 1, 6, 6)	100 109.9%	50.0 NaN	83.3 NaN
E-score <= 3.0 (n= 7, 5, 5)	14.3 15.7%	20.0 NaN	60.0 NaN
E-score >3.0 to 9.8 (n= 4, 4, 2)	75.0 82.4%	25.0 NaN	100 NaN
E-score >9.8 to 23.0 (n= 5, 4, 5)	60.0 65.9%	50.0 NaN	80.0 NaN
E-score >23.0 (n= 2, 8, 3)	50.0 54.9%	62.5 NaN	100 NaN
Joint space narrowing score <= 0.5 (n= 5, 7, 5)	20.0 22%	28.6 NaN	60.0 NaN
Joint space narrowing score >0.5 to 9.0 (n=5,0,6)	60.0 65.9%	0.0 NaN	100 NaN
Joint space narrowing score >9.0 to 23.5 (n=7,4,3)	57.1 62.7%	75.0 NaN	66.7 NaN
Joint space narrowing score >23.5 (n= 2, 9, 3)	50.0 54.9%	66.7 NaN	100 NaN
Erosion score <= 9.0 (n= 7, 0, 3)	42.9 47.1%	0.0 NaN	66.7 NaN
Erosion score >9.0 to 21.3 (n= 4, 3, 7)	25.0 27.5%	66.7 NaN	85.7 NaN
Erosion score >21.3 to 47.5 (n= 5, 6, 4)	40.0 44%	50.0 NaN	75.0 NaN
Erosion score >47.5 (n= 3, 8, 3)	100 109.9%	75.0 NaN	100 NaN
mTSS <= 10.0 (n= 5, 6, 4)	20.0 22%	16.7 NaN	50.0 NaN
mTSS >10.0 to 31.5 (n= 5, 3, 6)	60.0 65.9%	33.3 NaN	100 NaN
mTSS >31.5 to 70.0 (n= 7, 4, 4)	42.9 47.1%	75.0 NaN	75.0 NaN
mTSS >70.0 (n= 2, 9, 3)	100 109.9%	66.7 NaN	100 NaN

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Etanercept 50 mg - Period 1		Etanercept 50 mg - Period 2		Etanercept 25 mg - Period 2		Placebo - Period 2		Etanercept 50 mg - Period 3
Arm/Group Description	Etanercept 50 milligram (mg) subcutaneous (SC) injection once weekly along with methotrexate (MTX) 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or intramuscular (IM) injection, depending on the dose a participant was receiving at time of screening, for 8 weeks. Participants who maintained disease activity score based on 28-joints count (DAS28) less than or equal to (<=) 3.2 in Period 1 were randomized in Period 2.		Etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 more than [>] 5.1, or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 more than or equal to [>=] 1.2, or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits, or disease progression as determined by investigator) were reassigned to Period 3.		Etanercept 25 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.		Placebo matched to etanercept SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to treatment failure or Week 48/early termination. Participants who showed treatment failure (DAS28 >5.1 or DAS28 >3.2 but <=5.1 along with an increase from baseline in DAS28 >=1.2 or DAS28 >3.2 along with an increase from baseline >=0.6 but <1.2 on 2 consecutive visits or disease progression as determined by investigator) were reassigned to Period 3.		Participants, who showed treatment failure in Period 2, received etanercept 50 mg SC injection once weekly along with MTX 7.5 mg/week to 25 mg/week as a single dose or divided doses, as oral tablet or as SC or IM injection up to Week 48/early termination.
All Cause Mortality
	Etanercept 50 mg - Period 1		Etanercept 50 mg - Period 2		Etanercept 25 mg - Period 2		Placebo - Period 2		Etanercept 50 mg - Period 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Etanercept 50 mg - Period 1		Etanercept 50 mg - Period 2		Etanercept 25 mg - Period 2		Placebo - Period 2		Etanercept 50 mg - Period 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/91 (0%)		1/23 (4.3%)		1/27 (3.7%)		0/23 (0%)		1/43 (2.3%)
General disorders
Pyrexia	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Infections and infestations
Endometritis	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Etanercept 50 mg - Period 1		Etanercept 50 mg - Period 2		Etanercept 25 mg - Period 2		Placebo - Period 2		Etanercept 50 mg - Period 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/91 (29.7%)		16/23 (69.6%)		20/27 (74.1%)		7/23 (30.4%)		31/43 (72.1%)
Cardiac disorders
Arrhythmia	1/91 (1.1%)		0/23 (0%)		0/27 (0%)		1/23 (4.3%)		0/43 (0%)
Ventricular extrasystoles	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Endocrine disorders
Thyroiditis	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Eye disorders
Cataract	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Conjunctivitis	0/91 (0%)		0/23 (0%)		0/27 (0%)		1/23 (4.3%)		0/43 (0%)
Photokeratitis	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Gastrointestinal disorders
Diarrhoea	1/91 (1.1%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Constipation	0/91 (0%)		1/23 (4.3%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Haemorrhoids	0/91 (0%)		0/23 (0%)		2/27 (7.4%)		0/23 (0%)		0/43 (0%)
Gastritis	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Gastrooesophageal reflux disease	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Nausea	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Rectal haemorrhage	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Sigmoiditis	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		1/43 (2.3%)
Proctalgia	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
General disorders
Adverse drug reaction	1/91 (1.1%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Discomfort	1/91 (1.1%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Fatigue	1/91 (1.1%)		1/23 (4.3%)		1/27 (3.7%)		0/23 (0%)		1/43 (2.3%)
Pyrexia	0/91 (0%)		0/23 (0%)		3/27 (11.1%)		0/23 (0%)		0/43 (0%)
Chest pain	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Influenza like illness	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Injection site reaction	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Local swelling	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Oedema peripheral	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		1/43 (2.3%)
Pain	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Chest discomfort	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Infections and infestations
Nasopharyngitis	7/91 (7.7%)		6/23 (26.1%)		8/27 (29.6%)		2/23 (8.7%)		8/43 (18.6%)
Upper respiratory tract infection	2/91 (2.2%)		6/23 (26.1%)		3/27 (11.1%)		2/23 (8.7%)		9/43 (20.9%)
Bronchitis	1/91 (1.1%)		1/23 (4.3%)		1/27 (3.7%)		0/23 (0%)		1/43 (2.3%)
Conjunctivitis bacterial	1/91 (1.1%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Influenza	1/91 (1.1%)		1/23 (4.3%)		0/27 (0%)		1/23 (4.3%)		0/43 (0%)
Laryngitis	1/91 (1.1%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Pneumonia	1/91 (1.1%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Urinary tract infection	1/91 (1.1%)		0/23 (0%)		1/27 (3.7%)		1/23 (4.3%)		1/43 (2.3%)
Gastroenteritis	0/91 (0%)		0/23 (0%)		3/27 (11.1%)		0/23 (0%)		3/43 (7%)
Rhinitis	0/91 (0%)		1/23 (4.3%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Acute sinusitis	0/91 (0%)		0/23 (0%)		0/27 (0%)		1/23 (4.3%)		0/43 (0%)
Erythema migrans	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Herpes zoster	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Oral fungal infection	0/91 (0%)		0/23 (0%)		0/27 (0%)		1/23 (4.3%)		0/43 (0%)
Oral herpes	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Otitis externa	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Paronychia	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Tonsillitis	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Tooth infection	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Viral rhinitis	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Respiratory tract infection	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		3/43 (7%)
Localised infection	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		2/43 (4.7%)
Pharyngitis	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		2/43 (4.7%)
Skin infection	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		2/43 (4.7%)
Bacteriuria	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Borrelia infection	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Enterobiasis	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Eye infection	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Gastrointestinal infection	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Viral upper respiratory tract infection	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Injury, poisoning and procedural complications
Hand fracture	1/91 (1.1%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Ligament sprain	1/91 (1.1%)		1/23 (4.3%)		0/27 (0%)		1/23 (4.3%)		0/43 (0%)
Radius fracture	1/91 (1.1%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Injury	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Joint injury	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Limb injury	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Epicondylitis	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Investigations
Alanine aminotransferase increased	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
C-reactive protein increased	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Red blood cell sedimentation rate increased	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Neutrophil count decreased	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Metabolism and nutrition disorders
Vitamin d deficiency	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Musculoskeletal and connective tissue disorders
Back pain	3/91 (3.3%)		3/23 (13%)		1/27 (3.7%)		0/23 (0%)		2/43 (4.7%)
Arthralgia	2/91 (2.2%)		2/23 (8.7%)		3/27 (11.1%)		0/23 (0%)		1/43 (2.3%)
Neck pain	1/91 (1.1%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		1/43 (2.3%)
Periarthritis	1/91 (1.1%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Myalgia	0/91 (0%)		1/23 (4.3%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Osteoporosis	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		1/23 (4.3%)		0/43 (0%)
Pain in extremity	0/91 (0%)		1/23 (4.3%)		1/27 (3.7%)		0/23 (0%)		1/43 (2.3%)
Bursitis	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		1/43 (2.3%)
Exostosis	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Musculoskeletal pain	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Rheumatoid nodule	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Osteoarthritis	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Tenosynovitis	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of eyelid	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Seborrhoeic keratosis	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Nervous system disorders
Headache	0/91 (0%)		3/23 (13%)		1/27 (3.7%)		1/23 (4.3%)		1/43 (2.3%)
Dizziness	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Hypoaesthesia	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Migraine	0/91 (0%)		0/23 (0%)		0/27 (0%)		1/23 (4.3%)		0/43 (0%)
Psychiatric disorders
Depression	0/91 (0%)		0/23 (0%)		0/27 (0%)		1/23 (4.3%)		0/43 (0%)
Renal and urinary disorders
Haematuria	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Nephrolithiasis	0/91 (0%)		0/23 (0%)		0/27 (0%)		1/23 (4.3%)		0/43 (0%)
Urinary tract disorder	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Leukocyturia	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	2/91 (2.2%)		0/23 (0%)		2/27 (7.4%)		0/23 (0%)		1/43 (2.3%)
Rhinitis allergic	1/91 (1.1%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Chronic obstructive pulmonary disease	0/91 (0%)		0/23 (0%)		0/27 (0%)		1/23 (4.3%)		0/43 (0%)
Cough	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		2/43 (4.7%)
Epistaxis	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Throat irritation	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Skin and subcutaneous tissue disorders
Rash	1/91 (1.1%)		0/23 (0%)		1/27 (3.7%)		1/23 (4.3%)		2/43 (4.7%)
Eczema	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Psoriasis	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Erythema	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Intertrigo	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Lichen planus	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Surgical and medical procedures
Cataract operation	0/91 (0%)		0/23 (0%)		0/27 (0%)		1/23 (4.3%)		1/43 (2.3%)
Dental operation	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		0/43 (0%)
Toe operation	0/91 (0%)		0/23 (0%)		1/27 (3.7%)		0/23 (0%)		0/43 (0%)
Tooth extraction	0/91 (0%)		1/23 (4.3%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)
Vascular disorders
Hypertension	0/91 (0%)		0/23 (0%)		2/27 (7.4%)		0/23 (0%)		1/43 (2.3%)
Thrombophlebitis superficial	0/91 (0%)		0/23 (0%)		0/27 (0%)		0/23 (0%)		1/43 (2.3%)

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.