Study Evaluating the Efficacy and Safety of Etanercept and Methotrexate in Japanese Subjects With Rheumatoid Arthritis

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00445770
• Collaborator: (none)
• Enrollment: 550
• Locations: 41
• Arms: 3
• Duration (Months): 48
• Patients Per Site: 13.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the effects of etanercept (10 mg and 25 mg) compared with methotrexate (up to 8 mg per week) on the slowing of joint destruction.

Condition or Disease	Intervention/Treatment	Phase
Arthritis, Rheumatoid	Drug: Etanercept; Drug: Etanercept; Drug: Methotrexate	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 550 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Multicenter, Comparative Study Evaluating the Efficacy and Safety of Etanercept and Methotrexate in Japanese Subjects With Active Rheumatoid Arthritis
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Etanercept; 10 mg twice weekly, subcutaneous injection for 52 weeks
Experimental: 2	Drug: Etanercept; 25 mg, twice weekly, subcutaneous injection for 52 weeks
Active Comparator: 3	Drug: Methotrexate; up to 8 mg per week, oral dosing for 52 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52 [Week 52]

   mTSS = sum of erosion and 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 Baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represents improvement.

Secondary Outcome Measures

1. Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 [Week 24]

   mTSS = sum of erosion and 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 Baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represents improvement.

2. Change From Baseline in Erosion Score at Weeks 24 and 52 [Baseline, Week 24, and Week 52]

   Joint erosion score: erosion severity in 44 joints (16 per hand, 6 per foot). Each joint scored according to surface area involved, from 0 (no erosion) to 5 (extensive bone loss from more than one half of articulating bone). Because each side of foot joint was graded, maximum erosion score for foot joint was 10. Thus, maximum erosion score was 280. Change = score at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

3. Change From Baseline in Joint Space Narrowing (JSN) Score at Weeks 24 and 52 [Baseline, Week 24, and Week 52]

   JSN score: severity of JSN in 42 joints (15 per hand and 6 per foot), including subluxation, scored from 0 (no/normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation). Maximum JSN score was 168. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

4. Percentage of Participants With no Progression of Joint Destruction at Week 52 [Baseline and Week 52]

   Absence of joint destruction defined by 3 categories (mTSS change <=0.5, <=3.0, and <smallest detectable difference [SDD] where SDDs were scores >3.0). mTSS = sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score).

5. Change From Baseline in Swollen Joint Count at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

   American College of Rheumatology (ACR) swollen joint count was an assessment of 68 joints. Joints classified as either swollen or not swollen. Change = scores at observation minus score at Baseline, and total possible scores ranged from -68 to 68. An increase in swollen joints from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

6. Change From Baseline in Number of Painful Joints on Pressure or on Motion at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

   71 joints assessed by the investigator using criteria based on pressure and joint manipulation. Change = scores at observation minus score at Baseline, and total possible scores ranged from -71 to 71. An increase in tender joint count from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

7. Change From Baseline in Physician's Global Assessment of Symptoms at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

   Physician Global Assessment of symptoms, assessed using a 11-point rating scale, where 0=asymptomatic and 10=severe symptoms. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

8. Change From Baseline in Patient's Global Assessment at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

   Patient's Global Assessment of symptoms, assessed using a 11-point rating scale, where 0=asymptomatic and 10=severe symptoms. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

9. Change From Baseline in Mean Duration of Morning Stiffness at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

   Morning stiffness in and around the joints lasting at least 1 hour before maximal improvement. Change = scores at observation minus score at Baseline. An increase in stiffness duration from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

10. Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

    100 millimeter (mm) line (VAS) marked by participant. Intensity of pain range (over past week): 0mm = no pain to 100mm = worst possible pain. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

11. Change From Baseline in VAS for Participant General Health at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

    100mm line (VAS) marked by participant. Participants asked, "In general how would you rate your health over the last 2-3 weeks?" 0mm=very well to 100mm=extremely bad. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

12. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

    HAQ-DI: participant-reported assessment of ability to perform tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) hygiene; and 8) common activities over past week. Each item scored on 4-point Likert scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Change = scores at observation minus score at Baseline and total possible scores ranged from -3 to 3. An increase in score from baseline represented disease progression and/or joint worsening and a decrease represented improvement.

13. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

    ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).

14. Percentage of Participants With an ACR50 Response [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

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

15. Percentage of Participants With an ACR70 Response [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

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

16. Change From Baseline in Disease Activity Score (DAS) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

    DAS: weighted calculation of joint tenderness score (Ritchie Articular Index[RAI]), swollen joint count of 44 joints, natural logarithm (ln) of erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and general health (GH) using VAS. RAI defined as sum of 26 possible 0 to 3 tender scores. DAS = 0.53938 square root (√) (RAI) + 0.06465 (swollen joint count) + 0.330 (ln ESR) + 0.00722 (GH). Change from baseline = DAS at Week x minus Baseline DAS. Total DAS scores could range from 10 (worse outcome) to 0 (better outcome).

17. Change From Baseline in Disease Activity Score in 28 Joints (DAS28) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

    DAS based on 28 painful joint counts, 28 swollen joint counts, ESR, and GH. DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH. Change from baseline = DAS at Week x minus Baseline DAS. Total DAS scores could range from 10 (worse outcome) to 0 (better outcome).

18. Change From Baseline in C-reactive Protein (CRP) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

    CRP: marker of inflammation. Higher level consistent with inflammation. Normal CRP range: 0 to 1.0 milligrams per deciliter (mg/dL).

19. Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 [Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52]

    ESR: laboratory test that provided a non-specific measure of inflammation. The test assessed the rate at which red blood cells fell in a test tube and was measured in mm/hour. Normal range: 0-30mm/h. Higher rate consistent with inflammation.

Other Outcome Measures

1. Comparison of Etanercept Serum Concentrations Between the 10 mg and 25 mg Etanercept Doses [Weeks 12, 24, 52]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must be Japanese and live in Japan

• Must be age 20 to 75 years

• Diagnosed less than or equal to 10 years from time of first visit

Exclusion Criteria:

• Anyone who has received etanercept or TNF-inhibitors such as infliximab or adalimumab in the past

• Patient with other rheumatic diseases or conditions that could predispose the patient to infection

• Pregnant or lactating women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Nagoya	Aichi	Japan	460-0001
2	Pfizer Investigational Site	Nagoya	Aichi	Japan	4678602
3	Pfizer Investigational Site	Goshogawara	Aomori	Japan	037-0053
4	Pfizer Investigational Site	Asahi	Chiba	Japan	289-2511
5	Pfizer Investigational Site	Matsuyama	Ehime	Japan	790-8524
6	Pfizer Investigational Site	Iizuka	Fukuoka	Japan	820-8505
7	Pfizer Investigational Site	Kurume	Fukuoka	Japan	830-8543
8	Pfizer Investigational Site	Kurume	Fukuoka	Japan	8390863
9	Pfizer Investigational Site	Munakata	Fukuoka	Japan	8113431
10	Pfizer Investigational Site	Takasaki	Gunma	Japan	370-0053
11	Pfizer Investigational Site	Asahikawa	Hokkaido	Japan	078-8243
12	Pfizer Investigational Site	Sapporo	Hokkaido	Japan	060-0001
13	Pfizer Investigational Site	Kakogawa	Hyogo	Japan	6750009
14	Pfizer Investigational Site	Katoh	Hyougo	Japan	673-1462
15	Pfizer Investigational Site	Yuki	Ibaraki	Japan	307-0001
16	Pfizer Investigational Site	Komatsu	Ishikawa	Japan	923-8560
17	Pfizer Investigational Site	Kawasaki	Kanagawa	Japan	2120014
18	Pfizer Investigational Site	Sagamihara	Kanagawa	Japan	228-8522
19	Pfizer Investigational Site	Yokohama	Kanagawa	Japan	2310045
20	Pfizer Investigational Site	Sendai	Miyagi	Japan	9820032
21	Pfizer Investigational Site	Hyuga	Miyazaki	Japan	8830043
22	Pfizer Investigational Site	Sasebo	Nagasaki	Japan	857-1195
23	Pfizer Investigational Site	Ikoma	Nara	Japan	630-0293
24	Pfizer Investigational Site	Kawagoe	Saitama	Japan	350-8550
25	Pfizer Investigational Site	Tokorozawa	Saitama	Japan	359-1111
26	Pfizer Investigational Site	Bunkyo-ku	Tokyo	Japan	113-8549
27	Pfizer Investigational Site	Ota	Tokyo	Japan	1438541
28	Pfizer Investigational Site	Sumida-ku	Tokyo	Japan	130-0013
29	Pfizer Investigational Site	Fukui		Japan	9108561
30	Pfizer Investigational Site	Fukuoka		Japan	814-0002
31	Pfizer Investigational Site	Fukuoka		Japan	815-8588
32	Pfizer Investigational Site	Fukuoka		Japan	8150063
33	Pfizer Investigational Site	Hiroshima		Japan	7300031
34	Pfizer Investigational Site	Kagoshima		Japan	8900067
35	Pfizer Investigational Site	Kagoshima		Japan	891-0133
36	Pfizer Investigational Site	Kato city Fujita letter Higashiyama		Japan	944-25
37	Pfizer Investigational Site	Kumamoto		Japan	862-0976
38	Pfizer Investigational Site	Kumamoto		Japan	8620965
39	Pfizer Investigational Site	Miyagi		Japan	9810112
40	Pfizer Investigational Site	Miyazaki		Japan	8800122
41	Pfizer Investigational Site	Toyama		Japan	9338525

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.

• ClinicalTrials.gov Identifier: NCT00445770
• Other Study ID Numbers: 0881A1-315; B1801002
• First Posted: Mar 9, 2007
• Last Update Posted: Aug 15, 2011
• Last Verified: Aug 1, 2011

• Keywords provided by , ,: Rheumatoid Arthritis; Arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Etanercept; Methotrexate

Study Results

Participant Flow

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Period Title: Overall Study
STARTED	176	192	182
COMPLETED	123	157	151
NOT COMPLETED	53	35	31

Baseline Characteristics

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg	Total
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks	Total of all reporting groups
Overall Participants	176	192	182	550
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.40 (11.91)	51.46 (12.21)	51.81 (11.07)	51.24 (11.74)
Sex: Female, Male (Count of Participants)
Female	140 79.5%	154 80.2%	145 79.7%	439 79.8%
Male	36 20.5%	38 19.8%	37 20.3%	111 20.2%
modified Total Sharp Score (mTSS) (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	43.01 (46.78)	45.17 (38.75)	41.98 (41.51)	43.42 (42.28)
Erosion Score (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	25.09 (26.30)	26.66 (22.1)	25.23 (23.88)	25.69 (24.05)
Joint Space Narrowing (JSN) Score (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	17.92 (21.93)	18.50 (19.14)	16.75 (19.11)	17.73 (20.03)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52
Description	mTSS = sum of erosion and 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 Baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represents improvement.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Radiographic intent-to-treat (rITT) population: all participants who received at least 1 dose of the assigned test article and provided radiographic data for baseline and at least 1 post-baseline visit

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	171	190	181
Mean (Standard Error) [Scores on a scale]	9.82 (1.16)	5.19 (0.93)	3.33 (0.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	It was estimated that with 180 participants per group, there would be 81% power for the overall test. With this sample size and 0.05 (2-sided) type I error, there was 88% power to detect a 1.33 difference for the change of mTSS from baseline to 52 weeks between the etanercept 25 mg twice weekly group and Methotrexate group, assuming that the common standard deviation of the change of mTSS from baseline was 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Based on rank transformed data: rank of change = rank baseline+treatment +pooled study center+prior methotrexate use. If overall treatment effect statistically significant, 3 pairwise comparisons conducted, otherwise no further testing was made.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	An outcome showing that etanercept 10 mg was superior to methotrexate and the presence of numerical difference ≤0.5 mTSS units between etanercept 25 mg and etanercept 10 mg would support non-inferiority for the 2 etanercept treatments.
Statistical Test of Hypothesis	p-Value	0.2634
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24
Description	mTSS = sum of erosion and 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 Baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represents improvement.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

rITT

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	171	190	181
Mean (Standard Error) [Scores on a scale]	5.11 (0.58)	2.42 (0.48)	1.74 (0.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2248
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Change From Baseline in Erosion Score at Weeks 24 and 52
Description	Joint erosion score: erosion severity in 44 joints (16 per hand, 6 per foot). Each joint scored according to surface area involved, from 0 (no erosion) to 5 (extensive bone loss from more than one half of articulating bone). Because each side of foot joint was graded, maximum erosion score for foot joint was 10. Thus, maximum erosion score was 280. Change = score at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time Frame	Baseline, Week 24, and Week 52

Outcome Measure Data

Analysis Population Description

rITT

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	171	190	181
Change at Week 24	2.90 (0.33)	1.25 (0.29)	1.12 (0.30)
Change at Week 52	5.43 (0.64)	2.75 (0.57)	2.03 (0.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7260
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5717
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Change From Baseline in Joint Space Narrowing (JSN) Score at Weeks 24 and 52
Description	JSN score: severity of JSN in 42 joints (15 per hand and 6 per foot), including subluxation, scored from 0 (no/normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation). Maximum JSN score was 168. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time Frame	Baseline, Week 24, and Week 52

Outcome Measure Data

Analysis Population Description

rITT

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	171	190	181
Change at Week 24	2.21 (0.34)	1.18 (0.23)	0.62 (0.20)
Change at Week 52	4.39 (0.66)	2.44 (0.42)	1.31 (0.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0013
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0186
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1123
	Comments	P-values from ANCOVA model based on rank transformed data: rank of change = rank baseline + treatment + pooled study center + prior methotrexate use.
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Percentage of Participants With no Progression of Joint Destruction at Week 52
Description	Absence of joint destruction defined by 3 categories (mTSS change <=0.5, <=3.0, and <smallest detectable difference [SDD] where SDDs were scores >3.0). mTSS = sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score).
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

rITT

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	171	190	181
Progression ≤0.5	25.7 14.6%	45.3 23.6%	49.2 27%
Progression ≤3.0	46.8 26.6%	64.2 33.4%	68.0 37.4%
Progression ≤SDD	81.9 46.5%	88.9 46.3%	94.5 51.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52 for progression <=0.5
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Stratified by pooled study center and prior methotrexate use
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52 for progression <=0.5
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Stratified by pooled study center and prior methotrexate use
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52 for progression <=0.5
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3022
	Comments	Stratified by pooled study center and prior methotrexate use
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52 for progression <=3.0
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	Stratified by pooled study center and prior methotrexate use
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52 for progression <=3.0
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Stratified by pooled study center and prior methotrexate use
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52 for progression <=3.0
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3120
	Comments	Stratified by pooled study center and prior methotrexate use
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52 for progression <=SDD
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments	Stratified by pooled study center and prior methotrexate use.
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52 for progression <=SDD
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0285
	Comments	Stratified by pooled study center and prior methotrexate use
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52 for progression <=SDD
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0433
	Comments	Stratified by pooled study center and prior methotrexate use
	Method	Cochran-Mantel-Haenszel
	Comments

6. Secondary Outcome

Title	Change From Baseline in Swollen Joint Count at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Description	American College of Rheumatology (ACR) swollen joint count was an assessment of 68 joints. Joints classified as either swollen or not swollen. Change = scores at observation minus score at Baseline, and total possible scores ranged from -68 to 68. An increase in swollen joints from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

Modified ITT (mITT) population: participants who received at least 1 dose of the assigned test article; Last Observation Carried Forward (LOCF)

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Baseline	13.84 (7.81)	14.23 (8.97)	14.00 (8.80)
Change at Week 2	-3.39 (6.59)	-5.96 (6.94)	-5.02 (5.66)
Change at Week 4	-4.31 (6.68)	-7.03 (7.57)	-6.95 (6.35)
Change at Week 8	-5.76 (6.41)	-8.38 (7.77)	-7.91 (6.71)
Change at Week 12	-6.36 (6.97)	-9.05 (7.79)	-8.55 (6.72)
Change at Week 16	-6.59 (6.77)	-9.29 (7.93)	-8.78 (6.89)
Change at Week 20	-7.21 (7.47)	-9.68 (7.92)	-9.43 (7.45)
Change at Week 24	-7.06 (7.52)	-9.58 (7.98)	-9.57 (7.51)
Change at Week 32	-7.47 (7.74)	-9.89 (8.51)	-9.79 (7.62)
Change at Week 40	-7.93 (7.83)	-9.97 (8.53)	-10.05 (8.02)
Change at Week 48	-7.53 (8.26)	-9.87 (8.51)	-10.30 (8.41)
Change at Week 52	-7.53 (8.09)	-9.79 (8.58)	-10.49 (8.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0032
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1224
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8037
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5495
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4948
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4663
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9357
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7439
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8611
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6731
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2616
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1158
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

7. Secondary Outcome

Title	Change From Baseline in Number of Painful Joints on Pressure or on Motion at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Description	71 joints assessed by the investigator using criteria based on pressure and joint manipulation. Change = scores at observation minus score at Baseline, and total possible scores ranged from -71 to 71. An increase in tender joint count from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Baseline	17.12 (10.78)	16.30 (10.56)	17.48 (11.21)
Change at Week 2	-3.41 (7.48)	-6.81 (7.67)	-7.73 (7.81)
Change at Week 4	-5.58 (8.34)	-7.74 (9.21)	-8.65 (7.75)
Change at Week 8	-6.83 (8.30)	-9.27 (9.50)	-10.86 (9.07)
Change at Week 12	-8.42 (9.08)	-9.94 (9.63)	-11.36 (9.20)
Change at Week 16	-8.82 (9.44)	-10.70 (9.79)	-11.81 (9.29)
Change at Week 20	-9.15 (9.93)	-10.86 (9.85)	-12.38 (10.10)
Change at Week 24	-9.47 (10.30)	-10.94 (9.64)	-12.48 (9.81)
Change at Week 32	-9.91 (10.56)	-10.93 (9.75)	-12.97 (10.14)
Change at Week 40	-9.97 (10.43)	-11.07 (10.32)	-12.73 (10.87)
Change at Week 48	-10.45 (10.69)	-10.78 (9.84)	-13.17 (11.20)
Change at Week 52	-10.27 (10.60)	-10.75 (9.99)	-13.23 (11.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4237
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5738
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1606
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2412
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5882
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2257
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2075
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0050
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0461
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0101
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2351
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1179
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0214
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0790
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0168
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

8. Secondary Outcome

Title	Change From Baseline in Physician's Global Assessment of Symptoms at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Description	Physician Global Assessment of symptoms, assessed using a 11-point rating scale, where 0=asymptomatic and 10=severe symptoms. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Baseline	6.34 (1.98)	6.23 (1.79)	6.20 (1.86)
Week 2	-1.23 (1.67)	-2.20 (1.71)	-2.25 (1.71)
Week 4	-1.66 (1.81)	-2.65 (1.91)	-2.67 (1.90)
Week 8	-2.13 (2.05)	-3.02 (1.89)	-3.14 (1.89)
Week 12	-2.43 (2.13)	-3.30 (2.04)	-3.34 (1.94)
Week 16	-2.51 (2.21)	-3.46 (2.02)	-3.53 (1.99)
Week 20	-2.54 (2.29)	-3.51 (2.07)	-3.76 (2.01)
Week 24	-2.60 (2.43)	-3.52 (2.22)	-3.76 (2.07)
Week 32	-2.70 (2.36)	-3.54 (2.24)	-3.94 (2.09)
Week 40	-2.63 (2.41)	-3.62 (2.28)	-3.97 (2.27)
Week 48	-2.70 (2.52)	-3.59 (2.45)	-4.03 (2.20)
Week 52	-2.72 (2.40)	-3.68 (2.42)	-4.07 (2.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6337
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7407
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3473
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7529
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5216
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1078
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1280
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0291
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0729
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0271
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0453
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

9. Secondary Outcome

Title	Change From Baseline in Patient's Global Assessment at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Description	Patient's Global Assessment of symptoms, assessed using a 11-point rating scale, where 0=asymptomatic and 10=severe symptoms. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Baseline	6.01 (2.28)	6.12 (2.17)	5.95 (2.01)
Change at Week 2	-0.65 (1.95)	-1.81 (1.86)	-1.79 (1.82)
Change at Week 4	-1.11 (1.99)	-1.89 (2.06)	-1.91 (2.04)
Change at Week 8	-1.34 (2.31)	-2.37 (2.05)	-2.27 (2.13)
Change at Week 12	-1.63 (2.52)	-2.57 (2.22)	-2.38 (2.29)
Change at Week 16	-1.71 (2.45)	-2.55 (2.37)	-2.54 (2.40)
Change at Week 20	-1.85 (2.42)	-2.59 (2.36)	-2.69 (2.34)
Change at Week 24	-1.85 (2.66)	-2.65 (2.45)	-2.79 (2.45)
Change at Week 32	-1.89 (2.71)	-2.84 (2.44)	-2.92 (2.58)
Change at Week 40	-1.88 (2.68)	-2.89 (2.44)	-2.82 (2.67)
Change at Week 48	-1.97 (2.77)	-2.95 (2.46)	-2.98 (2.52)
Change at Week 52	-1.97 (2.70)	-3.04 (2.58)	-2.91 (2.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7488
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5680
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9241
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7146
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6574
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2936
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2179
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3704
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8047
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5277
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9371
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

10. Secondary Outcome

Title	Change From Baseline in Mean Duration of Morning Stiffness at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Description	Morning stiffness in and around the joints lasting at least 1 hour before maximal improvement. Change = scores at observation minus score at Baseline. An increase in stiffness duration from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Baseline	204.74 (338.70)	203.80 (304.92)	223.48 (344.75)
Change at Week 2	-46.39 (250.13)	-98.73 (259.91)	-108.37 (256.49)
Change at Week 4	-34.43 (249.33)	-94.87 (280.56)	-107.09 (255.06)
Change at Week 8	-52.53 (247.74)	-122.13 (304.33)	-127.55 (279.88)
Change at Week 12	-73.48 (236.69)	-128.02 (309.89)	-129.74 (284.58)
Change at Week 16	-78.60 (252.64)	-136.18 (318.85)	-148.13 (304.03)
Change at Week 20	-87.11 (276.35)	-137.18 (320.34)	-153.01 (314.41)
Change at Week 24	-89.94 (295.48)	-137.72 (317.24)	-143.03 (332.16)
Change at Week 32	-95.32 (330.07)	-137.26 (332.50)	-163.64 (320.36)
Change at Week 40	-97.76 (332.93)	-142.06 (335.44)	-157.52 (336.53)
Change at Week 48	-99.38 (306.33)	-136.23 (333.45)	-163.03 (326.06)
Change at Week 52	-98.98 (303.71)	-124.86 (361.03)	-171.36 (322.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0027
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8875
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9694
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7271
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0235
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0061
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6427
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0036
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0029
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9713
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0060
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0060
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9762
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0554
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0181
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6642
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0073
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0290
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5919
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0371
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0346
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9955
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0187
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0645
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5920
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0095
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2112
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1649
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

11. Secondary Outcome

Title	Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Description	100 millimeter (mm) line (VAS) marked by participant. Intensity of pain range (over past week): 0mm = no pain to 100mm = worst possible pain. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Baseline	54.91 (23.62)	54.37 (23.10)	52.63 (21.54)
Change at Week 2	-5.98 (19.11)	-18.85 (19.76)	-18.67 (20.32)
Change at Week 4	-10.64 (21.45)	-18.18 (22.95)	-19.16 (21.86)
Change at Week 8	-13.48 (25.21)	-23.09 (22.37)	-22.46 (22.34)
Change at Week 12	-16.95 (25.09)	-24.70 (22.74)	-24.01 (22.70)
Change at Week 16	-17.97 (26.61)	-24.41 (24.53)	-25.63 (25.04)
Change at Week 20	-19.53 (24.67)	-25.39 (24.01)	-26.52 (24.58)
Change at Week 24	-19.53 (27.02)	-26.86 (24.37)	-26.73 (24.99)
Change at Week 32	-19.72 (27.01)	-28.68 (25.00)	-28.10 (25.85)
Change at Week 40	-19.68 (27.35)	-28.81 (26.09)	-27.17 (25.26)
Change at Week 48	-20.85 (28.08)	-28.28 (25.04)	-28.77 (25.50)
Change at Week 52	-20.03 (27.74)	-29.08 (25.85)	-28.34 (25.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8972
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3736
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9324
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8982
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3180
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3302
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6563
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8894
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7826
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5343
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9313
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

12. Secondary Outcome

Title	Change From Baseline in VAS for Participant General Health at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Description	100mm line (VAS) marked by participant. Participants asked, "In general how would you rate your health over the last 2-3 weeks?" 0mm=very well to 100mm=extremely bad. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Baseline	58.37 (24.04)	58.71 (23.08)	55.70 (21.68)
Change at Week 2	-8.06 (19.00)	-21.07 (20.39)	-20.27 (22.08)
Change at Week 4	-13.51 (21.35)	-20.65 (23.18)	-20.69 (22.47)
Change at Week 8	-15.59 (24.92)	-26.16 (23.39)	-25.57 (22.59)
Change at Week 12	-20.05 (25.50)	-28.08 (24.87)	-26.34 (23.27)
Change at Week 16	-20.89 (27.29)	-28.37 (26.15)	-27.30 (24.73)
Change at Week 20	-22.35 (25.37)	-29.51 (25.05)	-29.16 (24.79)
Change at Week 24	-21.78 (27.55)	-30.23 (25.23)	-29.52 (25.39)
Change at Week 32	-22.87 (27.60)	-31.92 (24.91)	-31.11 (25.86)
Change at Week 40	-22.69 (28.18)	-31.49 (27.26)	-30.36 (25.54)
Change at Week 48	-23.76 (29.21)	-32.15 (26.01)	-31.27 (25.42)
Change at Week 52	-23.34 (28.48)	-32.25 (27.02)	-31.08 (26.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8044
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4652
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5612
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9749
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7290
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5004
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5727
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6713
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7663
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7073
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7973
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

13. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Description	HAQ-DI: participant-reported assessment of ability to perform tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) hygiene; and 8) common activities over past week. Each item scored on 4-point Likert scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Change = scores at observation minus score at Baseline and total possible scores ranged from -3 to 3. An increase in score from baseline represented disease progression and/or joint worsening and a decrease represented improvement.
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Baseline	1.01 (0.65)	1.17 (0.66)	1.06 (0.67)
Change at Week 2	-0.06 (0.36)	-0.30 (0.34)	-0.34 (0.41)
Change at Week 4	-0.12 (0.44)	-0.33 (0.39)	-0.40 (0.43)
Change at Week 8	-0.21 (0.49)	-0.46 (0.45)	-0.48 (0.46)
Change at Week 12	-0.29 (0.54)	-0.51 (0.48)	-0.52 (0.49)
Change at Week 16	-0.30 (0.55)	-0.52 (0.51)	-0.54 (0.52)
Change at Week 20	-0.32 (0.58)	-0.49 (0.53)	-0.57 (0.54)
Change at Week 24	-0.33 (0.62)	-0.54 (0.52)	-0.59 (0.55)
Change at Week 32	-0.33 (0.64)	-0.56 (0.52)	-0.59 (0.59)
Change at Week 40	-0.35 (0.64)	-0.56 (0.55)	-0.60 (0.60)
Change at Week 48	-0.34 (0.65)	-0.57 (0.57)	-0.59 (0.57)
Change at Week 52	-0.35 (0.64)	-0.56 (0.56)	-0.58 (0.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1053
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0144
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1851
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2883
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2221
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0147
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0201
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0036
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0789
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1903
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0048
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1059
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0018
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2589
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0040
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2326
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

14. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response
Description	ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Week 2	16.1 9.1%	54.0 28.1%	49.4 27.1%
Week 4	27.3 15.5%	55.5 28.9%	56.9 31.3%
Week 8	43.2 24.5%	68.1 35.5%	68.7 37.7%
Week 12	48.3 27.4%	70.2 36.6%	77.5 42.6%
Week 16	51.7 29.4%	73.8 38.4%	75.3 41.4%
Week 20	58.5 33.2%	75.4 39.3%	78.6 43.2%
Week 24	56.3 32%	77.0 40.1%	77.5 42.6%
Week 32	58.0 33%	79.1 41.2%	80.8 44.4%
Week 40	59.7 33.9%	78.5 40.9%	75.3 41.4%
Week 48	59.1 33.6%	76.4 39.8%	79.7 43.8%
Week 52	62.5 35.5%	75.9 39.5%	78.6 43.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4751
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4653
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7953
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0848
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6112
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3671
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7618
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4358
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6267
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3564
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0035
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4749
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

15. Secondary Outcome

Title	Percentage of Participants With an ACR50 Response
Description	ACR50 response: ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Week 2	2.3 1.3%	14.7 7.7%	16.0 8.8%
Week 4	4.0 2.3%	28.1 14.6%	22.5 12.4%
Week 8	15.3 8.7%	38.5 20.1%	35.7 19.6%
Week 12	23.9 13.6%	47.4 24.7%	42.3 23.2%
Week 16	26.1 14.8%	50.0 26%	44.0 24.2%
Week 20	30.7 17.4%	50.0 26%	50.5 27.7%
Week 24	32.4 18.4%	53.6 27.9%	54.4 29.9%
Week 32	34.7 19.7%	60.4 31.5%	59.3 32.6%
Week 40	36.9 21%	60.4 31.5%	58.8 32.3%
Week 48	39.2 22.3%	57.3 29.8%	57.7 31.7%
Week 52	36.9 21%	59.4 30.9%	62.1 34.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4376
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3947
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7378
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5680
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3978
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7229
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7236
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9719
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9349
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7226
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5512
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

16. Secondary Outcome

Title	Percentage of Participants With an ACR70 Response
Description	ACR70 response: ≥ 70% improvement in tender joint count; ≥ 70% improvement in swollen joint count; and ≥ 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Week 2	0 0%	4.2 2.2%	3.8 2.1%
Week 4	0.6 0.3%	7.8 4.1%	8.2 4.5%
Week 8	2.8 1.6%	15.1 7.9%	11.0 6%
Week 12	9.7 5.5%	21.9 11.4%	15.4 8.5%
Week 16	9.7 5.5%	17.7 9.2%	18.7 10.3%
Week 20	13.1 7.4%	25.0 13%	25.3 13.9%
Week 24	11.9 6.8%	25.5 13.3%	25.8 14.2%
Week 32	11.9 6.8%	28.1 14.6%	31.3 17.2%
Week 40	14.8 8.4%	31.3 16.3%	35.7 19.6%
Week 48	18.2 10.3%	34.4 17.9%	36.3 19.9%
Week 52	15.9 9%	33.9 17.7%	36.3 19.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0162
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0035
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8928
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6348
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0026
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4629
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0841
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1957
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0093
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0326
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7426
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0013
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6552
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6294
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4652
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2233
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6772
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6160
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by pooled study center and prior methotrexate use

17. Secondary Outcome

Title	Change From Baseline in Disease Activity Score (DAS) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Description	DAS: weighted calculation of joint tenderness score (Ritchie Articular Index[RAI]), swollen joint count of 44 joints, natural logarithm (ln) of erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and general health (GH) using VAS. RAI defined as sum of 26 possible 0 to 3 tender scores. DAS = 0.53938 square root (√) (RAI) + 0.06465 (swollen joint count) + 0.330 (ln ESR) + 0.00722 (GH). Change from baseline = DAS at Week x minus Baseline DAS. Total DAS scores could range from 10 (worse outcome) to 0 (better outcome).
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Baseline	4.07 (0.95)	4.03 (0.89)	4.05 (0.88)
Change at Week 2	-0.48 (0.64)	-1.09 (0.72)	-1.05 (0.70)
Change at Week 4	-0.69 (0.67)	-1.26 (0.90)	-1.26 (0.80)
Change at Week 8	-0.93 (0.79)	-1.48 (0.88)	-1.54 (0.86)
Change at Week 12	-1.12 (0.93)	-1.66 (0.97)	-1.65 (0.83)
Change at Week 16	-1.19 (0.98)	-1.69 (0.98)	-1.72 (0.88)
Change at Week 20	-1.28 (1.00)	-1.74 (0.97)	-1.80 (0.93)
Change at Week 24	-1.31 (1.09)	-1.77 (1.03)	-1.87 (0.98)
Change at Week 32	-1.37 (1.08)	-1.80 (1.02)	-1.95 (1.01)
Change at Week 40	-1.36 (1.08)	-1.90 (1.10)	-1.97 (1.02)
Change at Week 48	-1.46 (1.17)	-1.86 (1.13)	-2.02 (1.04)
Change at Week 52	-1.42 (1.14)	-1.86 (1.14)	-2.01 (1.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4929
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9693
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4139
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8905
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6877
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4511
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2786
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1230
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5061
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1354
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1734
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

18. Secondary Outcome

Title	Change From Baseline in Disease Activity Score in 28 Joints (DAS28) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Description	DAS based on 28 painful joint counts, 28 swollen joint counts, ESR, and GH. DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH. Change from baseline = DAS at Week x minus Baseline DAS. Total DAS scores could range from 10 (worse outcome) to 0 (better outcome).
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Baseline	5.84 (1.13)	5.75 (1.17)	5.82 (1.02)
Change at Week 2	-0.52 (0.75)	-1.32 (0.86)	-1.38 (0.88)
Change at Week 4	-0.77 (0.83)	-1.51 (1.05)	-1.60 (1.02)
Change at Week 8	-1.08 (0.99)	-1.79 (1.05)	-1.96 (1.11)
Change at Week 12	-1.33 (1.16)	-2.00 (1.15)	-2.09 (1.13)
Change at Week 16	-1.42 (1.24)	-2.08 (1.22)	-2.20 (1.17)
Change at Week 20	-1.54 (1.28)	-2.13 (1.24)	-2.31 (1.21)
Change at Week 24	-1.54 (1.34)	-2.20 (1.31)	-2.36 (1.27)
Change at Week 32	-1.63 (1.34)	-2.22 (1.29)	-2.45 (1.31)
Change at Week 40	-1.61 (1.36)	-2.31 (1.44)	-2.45 (1.33)
Change at Week 48	-1.75 (1.48)	-2.28 (1.51)	-2.51 (1.37)
Change at Week 52	-1.71 (1.44)	-2.25 (1.55)	-2.50 (1.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6417
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4698
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1214
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4654
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4006
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1636
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2635
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0965
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4437
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1663
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1049
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.
	Method	ANCOVA
	Comments

19. Secondary Outcome

Title	Change From Baseline in C-reactive Protein (CRP) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Description	CRP: marker of inflammation. Higher level consistent with inflammation. Normal CRP range: 0 to 1.0 milligrams per deciliter (mg/dL).
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Baseline	21.13 (22.30)	22.86 (29.77)	22.09 (24.17)
Change at Week 2	-3.08 (13.08)	-13.41 (19.53)	-15.62 (17.70)
Change at Week 4	-3.25 (15.82)	-11.05 (17.73)	-13.33 (16.58)
Change at Week 8	-4.19 (17.81)	-13.18 (20.74)	-15.17 (19.05)
Change at Week 12	-7.30 (18.00)	-13.04 (20.48)	-14.87 (20.36)
Change at Week 16	-6.51 (19.28)	-13.31 (20.73)	-15.15 (20.82)
Change at Week 20	-7.18 (21.29)	-12.21 (22.31)	-15.86 (20.23)
Change at Week 24	-6.31 (21.74)	-13.69 (21.26)	-16.28 (21.25)
Change at Week 32	-6.41 (21.68)	-13.45 (21.76)	-16.10 (21.38)
Change at Week 40	-6.23 (22.16)	-13.13 (22.47)	-15.38 (21.80)
Change at Week 48	-6.34 (22.18)	-13.01 (22.03)	-15.73 (22.44)
Change at Week 52	-5.20 (22.55)	-12.90 (22.96)	-15.08 (22.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0442
	Comments
	Method	ANCOVA
	Comments	P-values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0681
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0966
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1242
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1521
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0070
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0140
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0815
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0886
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1488
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0979
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1740
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior methotrexate use + treatment.

20. Secondary Outcome

Title	Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Description	ESR: laboratory test that provided a non-specific measure of inflammation. The test assessed the rate at which red blood cells fell in a test tube and was measured in mm/hour. Normal range: 0-30mm/h. Higher rate consistent with inflammation.
Time Frame	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52

Outcome Measure Data

Analysis Population Description

mITT; LOCF

Arm/Group Title	Methotrexate	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	176	192	182
Baseline	42.55 (28.24)	42.00 (29.44)	43.66 (27.64)
Change at Week 2	-1.86 (10.65)	-13.67 (13.07)	-16.91 (15.01)
Change at Week 4	-2.92 (11.78)	-13.26 (14.94)	-16.62 (16.03)
Change at Week 8	-5.50 (16.89)	-13.99 (17.39)	-18.01 (17.83)
Change at Week 12	-8.89 (17.38)	-15.18 (17.63)	-18.98 (19.04)
Change at Week 16	-8.56 (18.73)	-15.45 (18.54)	-19.78 (20.32)
Change at Week 20	-10.56 (20.45)	-15.68 (19.15)	-19.40 (20.18)
Change at Week 24	-9.88 (20.15)	-16.52 (20.09)	-20.01 (20.86)
Change at Week 32	-9.92 (20.51)	-16.06 (21.14)	-20.16 (21.54)
Change at Week 40	-9.33 (20.50)	-15.93 (21.47)	-18.28 (21.81)
Change at Week 48	-10.70 (20.93)	-15.61 (23.07)	-19.25 (21.77)
Change at Week 52	-10.22 (21.69)	-14.79 (23.06)	-18.85 (21.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior Methotrexate use + treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0274
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0344
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0293
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0452
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 16
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0313
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 20
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0781
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1279
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 32
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0807
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4180
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0061
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1615
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Etanercept 10 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0130
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Etanercept 10 mg, Etanercept 25 mg
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0948
	Comments
	Method	ANCOVA
	Comments	p-Values from ANCOVA model: change = baseline + pooled study center + prior MTX use + treatment.

21. Other Pre-specified Outcome

Title	Comparison of Etanercept Serum Concentrations Between the 10 mg and 25 mg Etanercept Doses
Time Frame	Weeks 12, 24, 52

Outcome Measure Data

Analysis Population Description

mITT; n = evaluable participants at the specified time point.

Arm/Group Title	Etanercept 10 mg	Etanercept 25 mg
Arm/Group Description	Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks	Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
Measure Participants	179	171
Week 12 (n=179, 164)	1012 (30.3)	2490 (79.6)
Week 24 (n=171, 171)	1094 (32.2)	2500 (79.3)
Week 52 (n=158, 149)	1097 (34.4)	2754 (136)

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an adverse event (AE) and a serious AE (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	Methotrexate		Etanercept 10 mg		Etanercept 25 mg
Arm/Group Description	Participants received 4 milligrams (mg) up to 8 mg orally (2.0 mg capsules), once weekly for 52 weeks and subcutaneous (SC) placebo injections twice weekly		Participants received 10 mg SC twice weekly and oral placebo capsules once weekly for 52 weeks		Participants received 25 mg twice weekly SC and oral placebo capsules once weekly for 52 weeks
All Cause Mortality
	Methotrexate		Etanercept 10 mg		Etanercept 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Methotrexate		Etanercept 10 mg		Etanercept 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/176 (5.7%)		8/192 (4.2%)		11/182 (6%)
Ear and labyrinth disorders
Sudden hearing loss	0/176 (0%)		0/192 (0%)		1/182 (0.5%)
Vertigo positional	0/176 (0%)		0/192 (0%)		1/182 (0.5%)
Endocrine disorders
Thyroiditis subacute	0/176 (0%)		0/192 (0%)		1/182 (0.5%)
Eye disorders
Retinal detachment	0/176 (0%)		1/192 (0.5%)		1/182 (0.5%)
Gastrointestinal disorders
Food poisoning	0/176 (0%)		0/192 (0%)		1/182 (0.5%)
General disorders
Pyrexia	0/176 (0%)		0/192 (0%)		1/182 (0.5%)
Infections and infestations
Appendicitis	1/176 (0.6%)		0/192 (0%)		0/182 (0%)
Pneumonia	0/176 (0%)		1/192 (0.5%)		0/182 (0%)
Urinary tract infection	0/176 (0%)		1/192 (0.5%)		0/182 (0%)
Injury, poisoning and procedural complications
Ankle fracture	1/176 (0.6%)		0/192 (0%)		0/182 (0%)
Femur fracture	0/176 (0%)		1/192 (0.5%)		0/182 (0%)
Fracture	1/176 (0.6%)		0/192 (0%)		0/182 (0%)
Spinal compression fracture	2/176 (1.1%)		0/192 (0%)		0/182 (0%)
Tendon rupture	0/176 (0%)		1/192 (0.5%)		0/182 (0%)
Ulna fracture	1/176 (0.6%)		0/192 (0%)		0/182 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/176 (0%)		1/192 (0.5%)		0/182 (0%)
Musculoskeletal pain	1/176 (0.6%)		0/192 (0%)		0/182 (0%)
Pain in extremity	1/176 (0.6%)		0/192 (0%)		0/182 (0%)
Rheumatoid arthritis	2/176 (1.1%)		1/192 (0.5%)		1/182 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/176 (0.6%)		0/192 (0%)		2/182 (1.1%)
Prostate cancer	1/176 (0.6%)		0/192 (0%)		0/182 (0%)
Nervous system disorders
Depressed level of consciousness	0/176 (0%)		1/192 (0.5%)		0/182 (0%)
Dizziness	0/176 (0%)		1/192 (0.5%)		0/182 (0%)
Occipital neuralgia	0/176 (0%)		0/192 (0%)		1/182 (0.5%)
Pregnancy, puerperium and perinatal conditions
Abortion	0/176 (0%)		0/192 (0%)		1/182 (0.5%)
Pregnancy	0/176 (0%)		0/192 (0%)		1/182 (0.5%)
Skin and subcutaneous tissue disorders
Urticaria	0/176 (0%)		1/192 (0.5%)		0/182 (0%)
Vascular disorders
Varicose vein	1/176 (0.6%)		0/192 (0%)		0/182 (0%)
Other (Not Including Serious) Adverse Events
	Methotrexate		Etanercept 10 mg		Etanercept 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	92/176 (52.3%)		106/192 (55.2%)		102/182 (56%)
Cardiac disorders
Palpitations	4/176 (2.3%)		0/192 (0%)		2/182 (1.1%)
Ear and labyrinth disorders
Vertigo	0/176 (0%)		5/192 (2.6%)		1/182 (0.5%)
Eye disorders
Conjunctivitis allergic	2/176 (1.1%)		0/192 (0%)		4/182 (2.2%)
Gastrointestinal disorders
Abdominal discomfort	4/176 (2.3%)		6/192 (3.1%)		0/182 (0%)
Abdominal pain upper	5/176 (2.8%)		3/192 (1.6%)		3/182 (1.6%)
Constipation	9/176 (5.1%)		6/192 (3.1%)		7/182 (3.8%)
Diarrhoea	5/176 (2.8%)		5/192 (2.6%)		10/182 (5.5%)
Gastritis	6/176 (3.4%)		3/192 (1.6%)		1/182 (0.5%)
Nausea	7/176 (4%)		4/192 (2.1%)		1/182 (0.5%)
Stomatitis	8/176 (4.5%)		8/192 (4.2%)		3/182 (1.6%)
Vomiting	1/176 (0.6%)		3/192 (1.6%)		4/182 (2.2%)
Dental caries	3/176 (1.7%)		4/192 (2.1%)		8/182 (4.4%)
Periodontitis	0/176 (0%)		1/192 (0.5%)		5/182 (2.7%)
General disorders
Pyrexia	6/176 (3.4%)		2/192 (1%)		8/182 (4.4%)
Hepatobiliary disorders
Hepatic function abnormal	6/176 (3.4%)		5/192 (2.6%)		3/182 (1.6%)
Infections and infestations
Bronchitis	5/176 (2.8%)		5/192 (2.6%)		6/182 (3.3%)
Cystitis	6/176 (3.4%)		4/192 (2.1%)		9/182 (4.9%)
Gastroenteritis	5/176 (2.8%)		1/192 (0.5%)		1/182 (0.5%)
Hordeolum	1/176 (0.6%)		2/192 (1%)		4/182 (2.2%)
Influenza	6/176 (3.4%)		4/192 (2.1%)		1/182 (0.5%)
Nasopharyngitis	43/176 (24.4%)		45/192 (23.4%)		37/182 (20.3%)
Oral herpes	2/176 (1.1%)		6/192 (3.1%)		2/182 (1.1%)
Otitis media	1/176 (0.6%)		4/192 (2.1%)		0/182 (0%)
Pharyngitis	12/176 (6.8%)		18/192 (9.4%)		15/182 (8.2%)
Pneumonia	0/176 (0%)		5/192 (2.6%)		2/182 (1.1%)
Upper respiratory tract infection	20/176 (11.4%)		20/192 (10.4%)		21/182 (11.5%)
Injury, poisoning and procedural complications
Contusion	4/176 (2.3%)		4/192 (2.1%)		8/182 (4.4%)
Investigations
Alanine aminotransferase increased	22/176 (12.5%)		12/192 (6.3%)		10/182 (5.5%)
Aspartate aminotransferase increased	18/176 (10.2%)		8/192 (4.2%)		8/182 (4.4%)
Blood alkaline phosphatase increased	3/176 (1.7%)		2/192 (1%)		5/182 (2.7%)
Blood pressure increased	3/176 (1.7%)		3/192 (1.6%)		4/182 (2.2%)
Blood urine present	2/176 (1.1%)		5/192 (2.6%)		2/182 (1.1%)
Transaminases increased	8/176 (4.5%)		5/192 (2.6%)		5/182 (2.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/176 (4%)		2/192 (1%)		1/182 (0.5%)
Nervous system disorders
Dizziness	1/176 (0.6%)		6/192 (3.1%)		3/182 (1.6%)
Headache	4/176 (2.3%)		5/192 (2.6%)		9/182 (4.9%)
Psychiatric disorders
Insomnia	9/176 (5.1%)		9/192 (4.7%)		2/182 (1.1%)
Respiratory, thoracic and mediastinal disorders
Cough	0/176 (0%)		4/192 (2.1%)		6/182 (3.3%)
Rhinitis allergic	3/176 (1.7%)		6/192 (3.1%)		1/182 (0.5%)
Skin and subcutaneous tissue disorders
Dermatitis	0/176 (0%)		2/192 (1%)		4/182 (2.2%)
Dermatitis contact	4/176 (2.3%)		3/192 (1.6%)		4/182 (2.2%)
Eczema	8/176 (4.5%)		7/192 (3.6%)		8/182 (4.4%)
Erythema	1/176 (0.6%)		4/192 (2.1%)		1/182 (0.5%)
Pruritus	3/176 (1.7%)		12/192 (6.3%)		5/182 (2.7%)
Rash	8/176 (4.5%)		10/192 (5.2%)		10/182 (5.5%)
Urticaria	2/176 (1.1%)		4/192 (2.1%)		1/182 (0.5%)
Vascular disorders
Hypertension	2/176 (1.1%)		4/192 (2.1%)		4/182 (2.2%)

Limitations/Caveats

Total Sharp Score and modified total Sharp Score were used interchangeably in the protocol and meant the same thing. In the statistical analysis plan and study results, mTSS was used consistently.

More Information

Certain Agreements

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

Wyeth 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.