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Trial record 1 of 1 for:    NCT00848354
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Open-Label Study Comparing Etanercept to Conventional Disease Modifying Antirheumatic Drug (DMARD) Therapy

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ClinicalTrials.gov Identifier: NCT00848354
Recruitment Status : Completed
First Posted : February 20, 2009
Results First Posted : April 19, 2012
Last Update Posted : January 18, 2016
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Biological: Phase 1: Etanercept
Drug: Phase 1: Methotrexate
Drug: Phase 2: Optional ETN, SSZ, HCQ, MTX
Drug: Phase 1: Conventiaonal DMARD
Enrollment 429
Recruitment Details The study consisted of 3 periods - Phase 1 (week 0-week 24), Phase 2 Year 1 (week 24-week 76), and Phase 2 Year 2 (week 76-week 128). 429 participants were randomly assigned to open label etanercept + methotrexate or open label conventional disease-modifying antirheumatic drug (DMARD) + methotrexate in a 2:1 allocation, respectively.
Pre-assignment Details Five participants (etanercept + methotrexate: 3, DMARD + methotrexate: 2) were randomized but did not receive study treatment. These participants were either randomized in error or withdrew consent before receiving the first dose. Phase 1 DMARD therapy was either hydroxychloroquine (HCQ) or sulfsalazine (SSZ), as selected by the investigator.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description Phase 1: Etanercept 50 mg injection subcutaneously (s.c.) once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen. Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Period Title: Phase 1
Started 281 [1] 143
Completed 269 129
Not Completed 12 14
Reason Not Completed
Adverse Event             5             4
Discontinuation of study by sponsor             2             1
Failed to return             0             1
Lost to Follow-up             1             1
Unspecified Reason             1             1
Protocol Violation             1             1
Withdrawal by Subject             2             4
Lack of Efficacy             0             1
[1]
One participant was randomized to the Etanercept + Methotrexate group but received SSZ in error.
Period Title: Phase 2 Year 1
Started 260 [1] 126 [2]
Completed 242 120
Not Completed 18 6
Reason Not Completed
Adverse Event             7             2
Death             1             0
Failed to Return             1             1
Lost to Follow-up             1             0
Unspecified Reason             3             0
Protocol Violation             4             1
Subject Request             1             2
[1]
Randomized Phase 1 treatment assignment. 9 participants discontinued between Phase 1 and Phase 2.
[2]
Randomized Phase 1 treatment assignment. 3 participants discontinued between Phase 1 and Phase 2.
Period Title: Phase 2 Year 2
Started 241 [1] 120 [2]
Completed 218 113
Not Completed 23 7
Reason Not Completed
Adverse Event             12             2
Death             2             0
Failed to return             3             0
Lost to Follow-up             1             3
Unspecified Reason             1             0
Protocol Violation             1             1
Subject Request             1             1
Unsatisfactory Response - Efficacy             2             0
[1]

Randomized Phase 1 treatment assignment.

1 participant discontinued between Year 1 and Year 2.

[2]
Randomized Phase 1 treatment assignment.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate Total
Hide Arm/Group Description Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen. Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen. Total of all reporting groups
Overall Number of Baseline Participants 281 143 424
Hide Baseline Analysis Population Description
The safety population included all randomized participant with documented use of at least 1 dose of test article - Baseline characteristics from Phase 1 CSR are provided.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 281 participants 143 participants 424 participants
48.4  (11.99) 48.7  (11.40) 48.5  (11.78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 281 participants 143 participants 424 participants
Female
248
  88.3%
129
  90.2%
377
  88.9%
Male
33
  11.7%
14
   9.8%
47
  11.1%
1.Primary Outcome
Title Percentage of Participants Achieving American College of Rheumatology 50 (ACR50) Response at Week 24
Hide Description ACR50 response: greater than or equal to 50 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 50 percent improvement from Baseline 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; participant's self-assessed disability (disability index of the Health Assessment Questionnaire; HAQ); and C-Reactive Protein (CRP).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT) population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. Last Observation carried forward (LOCF) method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Measure Type: Number
Unit of Measure: Percentage of participants
62.01 23.24
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Cochran-Mantel-Haenszel chi-square test, stratified by country, was used to calculate p-value. Assuming ACR50 response at Week 24 to be 23% in the DMARD combination therapy group and 37% in the etanercept + methotrexate group, a study enrolling 276 participants assigned to etanercept + methotrexate and 138 participants assigned to DMARD combination therapy has 80% power to reject the null hypothesis of no difference in response rates testing at the type I error = 0.05 level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in HAQ Score at Week 24
Hide Description HAQ: self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ score range: 0-3: without any difficulty: 0, with some difficulty: 1, with much difficulty: 2, unable to do: 3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25: normal functioning; 0.25-0.5: mild functional limitation; 0.5-1: moderate functional limitation; more than 1: significant functional limitation.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 141
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Baseline 1.55  (0.05) 1.51  (0.07)
Change at Week 24 -0.85  (0.04) -0.51  (0.06)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Analysis of covariance (ANCOVA) model with Baseline as covariate and factors for treatment and country as class variables was used to calculate p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method ANCOVA
Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score at Week 24
Hide Description The SF-36 is standardized 36-item survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health perception, vitality, and mental health. Domain scores range from 0-100, with greater scores reflecting better health status. Two additional overall summary scores - physical and mental component scores - were also obtained. Summary scores are standardized where the general population mean is 50 with a standard deviation of 10. Greater scores again indicate better health status.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 278 141
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Baseline, Vitality domain 12.46  (0.28) 12.39  (0.36)
Baseline, Mental component 40.50  (0.78) 40.41  (1.00)
Baseline, Physical component 30.42  (0.50) 30.18  (0.64)
Change at Week 24, Vitality domain 3.79  (0.27) 2.36  (0.35)
Change at Week 24, Mental component 7.33  (0.73) 3.32  (0.95)
Change at Week 24, Physical component 12.44  (0.65) 7.36  (0.84)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments ANCOVA model with Baseline as covariate and factors for treatment and country as class variables was used to calculate p-value. Statistical analysis presented above for vitality domain at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments ANCOVA model with Baseline as covariate and factors for treatment and country as class variables was used to calculate p-value. Statistical analysis presented above for mental component at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments ANCOVA model with Baseline as covariate and factors for treatment and country as class variables was used to calculate p-value. Statistical analysis presented above for physical component at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method ANCOVA
Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Van Der Heijde Modified Total Sharp Score (vdH mTSS), Annualized, at Week 24
Hide Description mTSS: sum of erosion and joint space narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Each x-ray visit included 4 films, each of which were read by 2 readers. The mTSS was calculated by the images scored for erosions and JSN. An increase in mTSS 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 Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Radiographic intent-to-treat (xITT) population included all participants who took at least 1 dose of study drug and had evaluable radiographic data at Baseline and Week 24.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 247 119
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Baseline 31.19  (4.06) 46.35  (5.35)
Week 24 0.40  (0.36) 1.37  (0.47)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments ANCOVA model on ranks of change in mTSS with treatment group and center main effects and the Baseline rank as covariate was used to calculate p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0270
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method ANCOVA
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Disease Activity Score Based on a 28-joint Count (DAS28) at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Description DAS28 calculated from the number of swollen joints and painful joints using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour; mm/hour) and the participant's general health using a 100 mm-visual analog scale (VAS). DAS28<3.2 indicates low disease activity and DAS28<2.6 remission.
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 2 (N: 275, 139) -1.50  (0.07) -0.67  (0.09)
Week 4 (N: 278, 142) -2.15  (0.08) -1.27  (0.10)
Week 8 (N: 279, 142) -2.59  (0.09) -1.54  (0.11)
Week 12 (N: 279, 142) -2.82  (0.09) -1.83  (0.12)
Week 16 (N: 279, 142) -3.01  (0.09) -1.84  (0.12)
Week 20 (N: 279, 142) -3.15  (0.09) -1.84  (0.12)
Week 24 (N: 279, 142) -3.20  (0.09) -1.70  (0.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments ANCOVA model with Baseline as covariate and factors for treatment and country as class variables was used to calculate p-values. ANCOVA was ran at each time-point shown, however as p-values obtained were identical, only one p-value is presented (which is applicable to each time-point - Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 - independently).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method ANCOVA
Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in DAS28 at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Description DAS28 calculated from the number of swollen joints and painful joints using the 28 joints count, the ESR (mm/hour) and the participant's general health using a 100 mm-VAS. DAS28<3.2 indicates low disease activity and DAS28<2.6 remission.
Time Frame Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (LOCF) was used. Phase 2 Year 1 (week 37-week 76)-sample size (Etanercept + Methotrexate, DMARD + Methotrexate: 260, 126) is different from Phase 2 Year 2 (week 89-week 128)-sample size (241, 120).
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 37 (N: 260, 126) -3.39  (1.34) -3.08  (1.29)
Week 50 (N: 260, 126) -3.42  (1.32) -3.33  (1.18)
Week 63 (N: 260, 126) -3.41  (1.31) -3.42  (1.16)
Week 76 (N: 260, 126) -3.38  (1.33) -3.36  (1.27)
Week 89 (N: 241, 120) -3.53  (1.34) -3.47  (1.34)
Week 102 (N: 241, 120) -3.43  (1.26) -3.47  (1.29)
Week 115 (N: 241, 120) -3.47  (1.31) -3.28  (1.37)
Week 128 (N: 241, 120) -3.41  (1.40) -3.51  (1.29)
7.Secondary Outcome
Title Summary of Changes in Therapy at the Beginning of Phase 2
Hide Description The investigators were allowed to alter each participant's therapy at the beginning of Phase 2. Continuations, discontinuations and additions made to Phase 1 treatment regimen were summarized.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used. One participant was randomized to etanercept but received SSZ in Phase 1.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Measure Type: Number
Unit of Measure: participants
No change: Etanercept 259 NA [1] 
No change: HCQ NA [2]  29
No change: Methotrexate 260 126
No change: SSZ NA [3]  11
Added Etanercept 1 105
Added HCQ 8 NA [4] 
Added SSZ 3 NA [5] 
Discontinued HCQ NA [2]  35
Discontinued SSZ 1 51
[1]
Participants did not receive etanercept during Phase 1.
[2]
Participants did not receive HCQ during Phase 1.
[3]
Participants did not receive SSZ during Phase 1.
[4]
Participants already received HCQ during Phase 1.
[5]
Participants already received SSZ during Phase 1.
8.Secondary Outcome
Title Percentage of Participants Achieving ACR50 Response at Week 2, Week 4, Week 8, Week 12, Week 16, and Week 20
Hide Description ACR50 response: greater than or equal to 50 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 50 percent improvement from Baseline 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; participant's self-assessed disability (disability index of HAQ); and CRP.
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, and Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (N: 278, 140) 15.83 2.86
Week 4 (N: 279, 142) 31.54 8.45
Week 8 (N: 279, 142) 42.29 16.90
Week 12 (N: 279, 142) 52.33 21.13
Week 16 (N: 279, 142) 56.27 24.65
Week 20 (N: 279, 142) 59.14 27.46
Week 24 (N: 279, 142) 62.01 23.24
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 2.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.39
Confidence Interval (2-Sided) 95%
2.25 to 18.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 4.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.99
Confidence Interval (2-Sided) 95%
2.62 to 9.49
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 8.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.6
Confidence Interval (2-Sided) 95%
2.19 to 5.94
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.10
Confidence Interval (2-Sided) 95%
2.57 to 6.53
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 16.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.93
Confidence Interval (2-Sided) 95%
2.51 to 6.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 20.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.82
Confidence Interval (2-Sided) 95%
2.46 to 5.93
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.39
Confidence Interval (2-Sided) 95%
3.41 to 8.53
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants Achieving ACR50 Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Description ACR50 response: greater than or equal to 50 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 50 percent improvement from Baseline 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; participant's self-assessed disability (disability index of HAQ); and ESR.
Time Frame Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (LOCF) was used. Phase 2 Year 1 (week 37-week 76)-sample size (Etanercept + Methotrexate, DMARD + Methotrexate: 260, 126) is different from Phase 2 Year 2 (week 89-week 128)-sample size (241, 120).
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Measure Type: Number
Unit of Measure: percentage of participants
Week 37 (N: 260, 126) 67.31 53.17
Week 50 (N: 260, 126) 65.77 60.32
Week 63 (N: 260, 126) 68.46 62.70
Week 76 (N: 260, 126) 67.31 58.73
Week 89 (N: 241, 120) 73.44 60.83
Week 102 (N: 241, 120) 73.44 61.67
Week 115 (N: 241, 120) 72.61 59.17
Week 128 (N: 241, 120) 70.54 65.00
10.Secondary Outcome
Title Percentage of Participants Achieving ACR20 Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Description ACR20 response: greater than or equal to 20 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 20 percent improvement from Baseline 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; participant's self-assessed disability (disability index of HAQ); and CRP.
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (N: 278, 140) 47.84 19.29
Week 4 (N: 279, 142) 63.80 34.51
Week 8 (N: 279, 142) 73.84 49.30
Week 12 (N: 279, 142) 79.57 54.93
Week 16 (N: 279, 142) 84.23 57.75
Week 20 (N: 279, 142) 84.59 58.45
Week 24 (N: 279, 142) 83.15 50.00
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 2.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.84
Confidence Interval (2-Sided) 95%
2.37 to 6.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 4.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.34
Confidence Interval (2-Sided) 95%
2.19 to 5.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 8.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.90
Confidence Interval (2-Sided) 95%
1.90 to 4.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.20
Confidence Interval (2-Sided) 95%
2.06 to 4.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 16.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.91
Confidence Interval (2-Sided) 95%
2.46 to 6.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 20.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.90
Confidence Interval (2-Sided) 95%
2.45 to 6.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.94
Confidence Interval (2-Sided) 95%
3.13 to 7.78
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percentage of Participants Achieving ACR20 Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Description ACR20 response: greater than or equal to 20 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 20 percent improvement from Baseline 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; participant's self-assessed disability (disability index of HAQ); and ESR.
Time Frame Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (LOCF) was used. Phase 2 Year 1 (week 37-week 76)-sample size (Etanercept + Methotrexate, DMARD + Methotrexate: 260, 126) is different from Phase 2 Year 2 (week 89-week 128)-sample size (241, 120).
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Measure Type: Number
Unit of Measure: percentage of participants
Week 37 (N: 260, 126) 86.92 80.95
Week 50 (N: 260, 126) 90.00 86.51
Week 63 (N: 260, 126) 88.85 91.27
Week 76 (N: 260, 126) 89.23 87.30
Week 89 (N: 241, 120) 90.87 89.17
Week 102 (N: 241, 120) 91.70 90.83
Week 115 (N: 241, 120) 90.04 83.33
Week 128 (N: 241, 120) 89.21 89.17
12.Secondary Outcome
Title Percentage of Participants Achieving ACR70 Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Description ACR70 response: greater than or equal to 50 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 70 percent improvement from Baseline 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; participant's self-assessed disability (disability index of HAQ); and CRP.
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (N: 278, 140) 3.60 0.71
Week 4 (N: 279, 142) 7.17 2.11
Week 8 (N: 279, 142) 16.13 3.52
Week 12 (N: 279, 142) 20.07 4.23
Week 16 (N: 279, 142) 27.60 9.15
Week 20 (N: 279, 142) 30.11 10.56
Week 24 (N: 279, 142) 34.77 11.27
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 2.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1086
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.19
Confidence Interval (2-Sided) 95%
0.66 to 40.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 4.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0392
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.58
Confidence Interval (2-Sided) 95%
1.04 to 12.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 8.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.27
Confidence Interval (2-Sided) 95%
2.04 to 13.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.69
Confidence Interval (2-Sided) 95%
2.39 to 13.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 16.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.78
Confidence Interval (2-Sided) 95%
2.02 to 7.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 20.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.65
Confidence Interval (2-Sided) 95%
2.02 to 6.60
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.20
Confidence Interval (2-Sided) 95%
2.36 to 7.46
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Percentage of Participants Achieving ACR70 Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Description ACR70 response: greater than or equal to 70 percent improvement from Baseline in tender joint count and swollen joint count; and greater than or equal to 70 percent improvement from Baseline 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; participant's self-assessed disability (disability index of HAQ); and ESR.
Time Frame Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (LOCF) was used. Phase 2 Year 1 (week 37-week 76)-sample size (Etanercept + Methotrexate, DMARD + Methotrexate: 260, 126) is different from Phase 2 Year 2 (week 89-week 128)-sample size (241, 120).
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Measure Type: Number
Unit of Measure: percentage of participants
Week 37 (N: 260, 126) 40.38 30.16
Week 50 (N: 260, 126) 45.00 32.54
Week 63 (N: 260, 126) 39.62 34.13
Week 76 (N: 260, 126) 41.92 34.13
Week 89 (N: 241, 120) 53.11 38.33
Week 102 (N: 241, 120) 48.96 36.67
Week 115 (N: 241, 120) 48.55 35.00
Week 128 (N: 241, 120) 48.96 40.00
14.Secondary Outcome
Title Change From Baseline in Disease Activity Score (DAS) at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Description DAS calculated from number of painful joints using the ritchie articular index (RAI), number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant's general health using a 100 mm-VAS. DAS≤2.4 indicates low disease activity and DAS<1.6 remission.
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 2 (N: 274, 139) -1.42  (0.07) -0.65  (0.09)
Week 4 (N: 277, 142) -2.07  (0.07) -1.29  (0.09)
Week 8 (N: 278, 142) -2.45  (0.07) -1.55  (0.10)
Week 12 (N: 278, 142) -2.67  (0.08) -1.79  (0.10)
Week 16 (N: 278, 142) -2.82  (0.08) -1.86  (0.10)
Week 20 (N: 278, 142) -2.95  (0.08) -1.85  (0.10)
Week 24 (N: 278, 142) -2.97  (0.08) -1.72  (0.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments ANCOVA model with Baseline as covariate and factors for treatment and country as class variables was used to calculate p-values. ANCOVA was ran at each time-point shown, however as p-values obtained were identical, only one p-value is presented (which is applicable to each time-point - Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 - independently).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method ANCOVA
Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline in DAS at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Description DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant's general health using a 100 mm-VAS. DAS≤2.4 indicates low disease activity and DAS<1.6 remission.
Time Frame Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (LOCF) was used. Phase 2 Year 1 (week 37-week 76)-sample size (Etanercept + Methotrexate, DMARD + Methotrexate: 260, 126) is different from Phase 2 Year 2 (week 89-week 128)-sample size (241, 120).
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 37 (N: 259, 126) -3.13  (1.28) -2.94  (1.25)
Week 50 (N: 259, 126) -3.21  (1.24) -3.19  (1.12)
Week 63 (N: 259, 126) -3.17  (1.19) -3.26  (1.19)
Week 76 (N: 259, 126) -3.18  (1.28) -3.24  (1.23)
Week 89 (N: 239, 120) -3.29  (1.27) -3.26  (1.38)
Week 102 (N: 239, 120) -3.24  (1.23) -3.31  (1.31)
Week 115 (N: 239, 120) -3.28  (1.22) -3.18  (1.41)
Week 128 (N: 239, 120) -3.23  (1.32) -3.35  (1.38)
16.Secondary Outcome
Title Percentage of Participants Achieving DAS<2.4 (Low Disease Activity) Response at Week 24
Hide Description DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant's general health using a 100 mm-VAS. DAS<2.4: low disease activity, DAS<1.6: remission.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 278 142
Measure Type: Number
Unit of Measure: percentage of participants
61.51 20.42
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.23
Confidence Interval (2-Sided) 95%
3.88 to 10.00
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Percentage of Participants Achieving DAS<1.6 (Remission) Response at Week 24
Hide Description DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant's general health using a 100 mm-VAS. DAS<2.4: low disease activity, DAS<1.6: remission.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 278 142
Measure Type: Number
Unit of Measure: percentage of participants
28.78 4.93
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 7.79
Confidence Interval (2-Sided) 95%
3.49 to 17.39
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Percentage of Participants Achieving DAS Improvement of ≥0.6 From Baseline at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Description DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant's general health using a 100 mm-VAS. DAS<2.4: low disease activity, DAS<1.6: remission.
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (N: 274, 139) 79.93 53.24
Week 4 (N: 277, 142) 90.97 66.90
Week 8 (N: 278, 142) 95.68 78.87
Week 12 (N: 278, 142) 95.32 81.69
Week 16 (N: 278, 142) 96.76 83.10
Week 20 (N: 278, 142) 97.12 83.10
Week 24 (N: 278, 142) 96.04 76.06
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 2.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.50
Confidence Interval (2-Sided) 95%
2.24 to 5.46
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 4.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.99
Confidence Interval (2-Sided) 95%
2.91 to 8.55
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 8.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.94
Confidence Interval (2-Sided) 95%
2.93 to 12.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.57
Confidence Interval (2-Sided) 95%
2.27 to 9.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 16.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.08
Confidence Interval (2-Sided) 95%
2.74 to 13.48
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 20.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.86
Confidence Interval (2-Sided) 95%
3.00 to 15.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 7.64
Confidence Interval (2-Sided) 95%
3.74 to 15.63
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Percentage of Participants Achieving DAS Improvement of ≥0.6 From Baseline at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Description DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant's general health using a 100 mm-VAS. DAS<2.4: low disease activity, DAS<1.6: remission.
Time Frame Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (LOCF) was used. Phase 2 Year 1 (week 37-week 76)-sample size (Etanercept + Methotrexate, DMARD + Methotrexate: 260, 126) is different from Phase 2 Year 2 (week 89-week 128)-sample size (241, 120).
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Measure Type: Number
Unit of Measure: percentage of participants
Week 37 (N: 259, 126) 98.07 96.83
Week 50 (N: 259, 126) 98.46 98.41
Week 63 (N: 259, 126) 96.91 99.21
Week 76 (N: 259, 126) 96.53 98.41
Week 89 (N: 239, 120) 97.49 98.33
Week 102 (N: 239, 120) 98.74 98.33
Week 115 (N: 239, 120) 98.33 96.67
Week 128 (N: 239, 120) 97.07 99.17
20.Secondary Outcome
Title Percentage of Participants Achieving DAS Improvement of ≥1.2 From Baseline at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Description DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant's general health using a 100 mm-VAS. DAS<2.4: low disease activity, DAS<1.6: remission.
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (N: 274, 139) 57.66 30.22
Week 4 (N: 277, 142) 78.34 45.07
Week 8 (N: 278, 142) 84.89 58.45
Week 12 (N: 278, 142) 87.77 64.79
Week 16 (N: 278, 142) 92.09 67.61
Week 20 (N: 278, 142) 91.73 66.90
Week 24 (N: 278, 142) 91.01 60.56
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 2.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.15
Confidence Interval (2-Sided) 95%
2.04 to 4.86
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 4.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.41
Confidence Interval (2-Sided) 95%
2.85 to 6.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 8.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.99
Confidence Interval (2-Sided) 95%
2.50 to 6.38
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.90
Confidence Interval (2-Sided) 95%
2.37 to 6.41
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 16.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.58
Confidence Interval (2-Sided) 95%
3.19 to 9.76
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 20.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.49
Confidence Interval (2-Sided) 95%
3.16 to 9.52
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.59
Confidence Interval (2-Sided) 95%
3.87 to 11.21
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Percentage of Participants Achieving DAS Improvement of ≥1.2 From Baseline at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Description DAS calculated from number of painful joints using RAI, number of swollen joints using the same 44 joints as in RAI, ESR (mm/hour) and participant's general health using a 100 mm-VAS. DAS<2.4: low disease activity, DAS<1.6: remission.
Time Frame Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (LOCF) was used. Phase 2 Year 1 (week 37-week 76)-sample size (Etanercept + Methotrexate, DMARD + Methotrexate: 260, 126) is different from Phase 2 Year 2 (week 89-week 128)-sample size (241, 120).
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Measure Type: Number
Unit of Measure: percentage of participants
Week 37 (N: 259, 126) 95.37 89.68
Week 50 (N: 259, 126) 96.53 96.03
Week 63 (N: 259, 126) 95.75 95.24
Week 76 (N: 259, 126) 94.21 96.03
Week 89 (N: 239, 120) 94.56 94.17
Week 102 (N: 239, 120) 95.40 97.50
Week 115 (N: 239, 120) 97.49 94.17
Week 128 (N: 239, 120) 94.14 95.83
22.Secondary Outcome
Title Percentage of Participants Achieving Moderate/Good DAS-Based European League Against Rheumatism (EULAR) Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Description

DAS-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Moderate or good DAS-based EULAR response was defined as:

  • DAS-value ≤3.7 and DAS-improvement from Baseline >0.6
  • DAS-value >3.7 and DAS-improvement from Baseline >1.2
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (N: 274, 139) 66.42 35.97
Week 4 (N: 277, 142) 84.12 52.11
Week 8 (N: 278, 142) 89.93 64.08
Week 12 (N: 278, 142) 91.01 69.72
Week 16 (N: 278, 142) 93.88 72.54
Week 20 (N: 278, 142) 94.6 73.94
Week 24 (N: 278, 142) 92.45 65.49
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 2.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.52
Confidence Interval (2-Sided) 95%
2.30 to 5.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 4.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.87
Confidence Interval (2-Sided) 95%
3.07 to 7.71
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 8.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.00
Confidence Interval (2-Sided) 95%
2.98 to 8.41
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.40
Confidence Interval (2-Sided) 95%
2.55 to 7.58
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 16.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.81
Confidence Interval (2-Sided) 95%
3.15 to 10.74
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 20.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.18
Confidence Interval (2-Sided) 95%
3.25 to 11.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.45
Confidence Interval (2-Sided) 95%
3.67 to 11.33
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Percentage of Participants Achieving Moderate/Good Disease DAS-Based EULAR Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Description

DAS-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Moderate or good DAS-based EULAR response was defined as:

  • DAS-value ≤3.7 and DAS-improvement from Baseline >0.6
  • DAS-value >3.7 and DAS-improvement from Baseline >1.2
Time Frame Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (LOCF) was used. Phase 2 Year 1 (week 37-week 76)-sample size (Etanercept + Methotrexate, DMARD + Methotrexate: 260, 126) is different from Phase 2 Year 2 (week 89-week 128)-sample size (241, 120).
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Measure Type: Number
Unit of Measure: percentage of participants
Week 37 (N: 259, 126) 97.3 93.65
Week 50 (N: 259, 126) 97.3 97.62
Week 63 (N: 259, 126) 96.53 98.41
Week 76 (N: 259, 126) 95.37 97.62
Week 89 (N: 239, 120) 97.07 97.50
Week 102 (N: 239, 120) 97.49 97.50
Week 115 (N: 239, 120) 98.33 96.67
Week 128 (N: 239, 120) 96.23 98.33
24.Secondary Outcome
Title Percentage of Participants Achieving Good DAS-Based EULAR Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Description DAS-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Good DAS-based EULAR response was defined as: DAS-value ≤2.4 and DAS-improvement from Baseline >1.2.
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (N: 274, 139) 8.39 2.88
Week 4 (N: 277, 142) 24.55 7.75
Week 8 (N: 278, 142) 39.21 15.49
Week 12 (N: 278, 142) 48.2 22.54
Week 16 (N: 278, 142) 56.12 22.54
Week 20 (N: 278, 142) 58.99 24.65
Week 24 (N: 278, 142) 61.15 20.42
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 2.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0349
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.09
Confidence Interval (2-Sided) 95%
1.05 to 9.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 4.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.87
Confidence Interval (2-Sided) 95%
1.98 to 7.60
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 8.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.52
Confidence Interval (2-Sided) 95%
2.10 to 5.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.20
Confidence Interval (2-Sided) 95%
2.02 to 5.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 16.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.40
Confidence Interval (2-Sided) 95%
2.78 to 6.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 20.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.40
Confidence Interval (2-Sided) 95%
2.80 to 6.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.13
Confidence Interval (2-Sided) 95%
3.82 to 9.85
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Percentage of Participants Achieving Good DAS-Based EULAR Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Description DAS-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Good DAS-based EULAR response was defined as: DAS-value ≤2.4 and DAS-improvement from Baseline >1.2.
Time Frame Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (LOCF) was used. Phase 2 Year 1 (week 37-week 76)-sample size (Etanercept + Methotrexate, DMARD + Methotrexate: 260, 126) is different from Phase 2 Year 2 (week 89-week 128)-sample size (241, 120).
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Measure Type: Number
Unit of Measure: percentage of participants
Week 37 (N: 259, 126) 73.36 56.35
Week 50 (N: 259, 126) 72.2 69.05
Week 63 (N: 259, 126) 72.97 70.63
Week 76 (N: 259, 126) 73.75 64.29
Week 89 (N: 239, 120) 76.57 68.33
Week 102 (N: 239, 120) 77.41 70.83
Week 115 (N: 239, 120) 76.57 66.67
Week 128 (N: 239, 120) 75.73 70.00
26.Secondary Outcome
Title Percentage of Participants Achieving Moderate/Good DAS28-Based EULAR Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Description

DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Moderate or good DAS28-based EULAR response was defined as:

  • DAS28-value ≤5.1 and DAS28-improvement from Baseline >0.6
  • DAS28-value >5.1 and DAS28-improvement from Baseline >1.2
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (N: 275, 139) 64 29.5
Week 4 (N: 278, 142) 81.29 48.59
Week 8 (N: 279, 142) 88.89 60.56
Week 12 (N: 279, 142) 91.4 64.79
Week 16 (N: 279, 142) 93.91 68.31
Week 20 (N: 279, 142) 94.62 67.61
Week 24 (N: 279, 142) 91.76 64.79
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 2.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.25
Confidence Interval (2-Sided) 95%
2.74 to 6.60
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 4.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.60
Confidence Interval (2-Sided) 95%
2.94 to 7.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 8.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.21
Confidence Interval (2-Sided) 95%
3.15 to 8.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.77
Confidence Interval (2-Sided) 95%
3.36 to 9.93
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 16.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 7.15
Confidence Interval (2-Sided) 95%
3.91 to 13.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 20.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 8.43
Confidence Interval (2-Sided) 95%
4.50 to 15.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.05
Confidence Interval (2-Sided) 95%
3.50 to 10.47
Estimation Comments [Not Specified]
27.Secondary Outcome
Title Percentage of Participants Achieving Moderate/Good DAS28-Based EULAR Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Description

DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Moderate or good DAS28-based EULAR response was defined as:

  • DAS28-value ≤5.1 and DAS28-improvement from Baseline >0.6
  • DAS28-value >5.1 and DAS28-improvement from Baseline >1.2
Time Frame Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (LOCF) was used. Phase 2 Year 1 (week 37-week 76)-sample size (Etanercept + Methotrexate, DMARD + Methotrexate: 260, 126) is different from Phase 2 Year 2 (week 89-week 128)-sample size (241, 120).
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Measure Type: Number
Unit of Measure: percentage of participants
Week 37 (N: 260, 126) 95.77 93.65
Week 50 (N: 260, 126) 96.15 95.24
Week 63 (N: 260, 126) 96.15 96.83
Week 76 (N: 260, 126) 95 96.83
Week 89 (N: 241, 120) 95.85 96.67
Week 102 (N: 241, 120) 95.02 96.67
Week 115 (N: 241, 120) 95.44 93.33
Week 128 (N: 241, 120) 92.95 97.50
28.Secondary Outcome
Title Percentage of Participants Achieving Good DAS28-Based EULAR Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Description DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Good DAS28-based EULAR response was defined as: DAS28-value ≤3.2 and DAS28-improvement from Baseline >1.2.
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (N: 275, 139) 5.09 0.72
Week 4 (N: 278, 142) 10.79 4.93
Week 8 (N: 279, 142) 22.22 9.15
Week 12 (N: 279, 142) 30.11 12.68
Week 16 (N: 279, 142) 38.35 16.9
Week 20 (N: 279, 142) 43.01 15.49
Week 24 (N: 279, 142) 46.95 11.97
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 2.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0250
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 7.40
Confidence Interval (2-Sided) 95%
0.96 to 56.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 4.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0466
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.33
Confidence Interval (2-Sided) 95%
1.00 to 5.45
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 8.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.84
Confidence Interval (2-Sided) 95%
1.50 to 5.36
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.97
Confidence Interval (2-Sided) 95%
1.70 to 5.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 16.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.06
Confidence Interval (2-Sided) 95%
1.85 to 5.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 20.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.12
Confidence Interval (2-Sided) 95%
2.47 to 6.87
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.51
Confidence Interval (2-Sided) 95%
3.72 to 11.38
Estimation Comments [Not Specified]
29.Secondary Outcome
Title Percentage of Participants Achieving Good DAS28-Based EULAR Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Description DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from Baseline and the level of disease activity reached. Good DAS28-based EULAR response was defined as: DAS28-value ≤3.2 and DAS28-improvement from Baseline >1.2.
Time Frame Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (LOCF) was used. Phase 2 Year 1 (week 37-week 76)-sample size (Etanercept + Methotrexate, DMARD + Methotrexate: 260, 126) is different from Phase 2 Year 2 (week 89-week 128)-sample size (241, 120).
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Measure Type: Number
Unit of Measure: percentage of participants
Week 37 (N: 260, 126) 53.08 37.3
Week 50 (N: 260, 126) 54.62 45.24
Week 63 (N: 260, 126) 55.38 50.79
Week 76 (N: 260, 126) 56.92 44.44
Week 89 (N: 241, 120) 60.58 50.83
Week 102 (N: 241, 120) 56.43 50.00
Week 115 (N: 241, 120) 56.85 45.83
Week 128 (N: 241, 120) 57.68 55.00
30.Secondary Outcome
Title Percentage of Participants Achieving DAS28<2.6 (Remission) Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Description DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, ESR (mm/hour) and participant's general health using a 100 mm-VAS. DAS28<3.2: low disease activity, DAS28<2.6: remission.
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (N: 275, 139) 1.45 0
Week 4 (N: 278, 142) 4.32 2.11
Week 8 (N: 279, 142) 10.04 4.23
Week 12 (N: 279, 142) 14.7 5.63
Week 16 (N: 279, 142) 20.43 5.63
Week 20 (N: 279, 142) 28.67 6.34
Week 24 (N: 279, 142) 25.09 3.52
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 2.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3054
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 4.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4044
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.09
Confidence Interval (2-Sided) 95%
0.58 to 7.53
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 8.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0388
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.53
Confidence Interval (2-Sided) 95%
1.02 to 6.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 12.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0059
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.89
Confidence Interval (2-Sided) 95%
1.31 to 6.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 16.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.30
Confidence Interval (2-Sided) 95%
1.99 to 9.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 20.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.94
Confidence Interval (2-Sided) 95%
2.88 to 12.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 9.18
Confidence Interval (2-Sided) 95%
3.61 to 23.32
Estimation Comments [Not Specified]
31.Secondary Outcome
Title Percentage of Participants Achieving DAS28<2.6 (Remission) Response at Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Description DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, ESR (mm/hour) and participant's general health using a 100 mm-VAS. DAS28<3.2: low disease activity, DAS28<2.6: remission.
Time Frame Week 37, Week 50, Week 63, Week 76, Week 89, Week 102, Week 115, and Week 128
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (LOCF) was used. Phase 2 Year 1 (week 37-week 76)-sample size (Etanercept + Methotrexate, DMARD + Methotrexate: 260, 126) is different from Phase 2 Year 2 (week 89-week 128)-sample size (241, 120).
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 260 126
Measure Type: Number
Unit of Measure: percentage of participants
Week 37 (N: 260, 126) 33.85 22.22
Week 50 (N: 260, 126) 36.54 26.19
Week 63 (N: 260, 126) 38.46 26.19
Week 76 (N: 260, 126) 33.46 23.02
Week 89 (N: 241, 120) 45.64 34.17
Week 102 (N: 241, 120) 36.93 36.67
Week 115 (N: 241, 120) 39.42 30.00
Week 128 (N: 241, 120) 39.83 33.33
32.Secondary Outcome
Title Percentage of Participants Achieving DAS28<3.2 (Low Disease Activity) Response at Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Description DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, ESR (mm/hour) and participant's general health using a 100 mm-VAS. DAS28<3.2: low disease activity, DAS28<2.6: remission.
Time Frame Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who took at least 1 dose of study drug and had at least 1 post-randomization visit that included evaluation of tender and swollen joints and at least 3 of other 5 variables required to calculate ACR50. LOCF method was used.
Arm/Group Title Etanercept + Methotrexate DMARD + Methotrexate
Hide Arm/Group Description:
Phase 1: Etanercept 50 mg injection s.c. once weekly along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on etanercept and methotrexate, or a non-biologic DMARD the investigator preferred in accordance with the local label (SSZ or HCQ) could be added in exchange for or in addition to etanercept. Methotrexate could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Phase 1: Conventional DMARD combination therapy (SSZ or HCQ) tablets administered as per local prescribing practice, along with methotrexate tablet (7.5-25 mg) orally once weekly either in single dose or in 2 divided doses for 24 weeks. Phase 2: During the optional Phase 2-period (week 24-week 128), the participants could remain on DMARD (SSZ or HCQ) and methotrexate, or a DMARD the investigator preferred in accordance with the local label (HCQ, SSZ, and/or etanercept) could be added in exchange for or in addition to the Phase 1 DMARD (SSZ or HCQ). Methotrexate and the DMARD administered in Phase 1 could be continued, discontinued or titrated. Phase 1 reporting groups were used also for Phase 2 data, regardless of the participant's Phase 2 treament regimen.
Overall Number of Participants Analyzed 279 142
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (N: 275, 139) 5.09 0.72
Week 4 (N: 278, 142) 10.79 4.93
Week 8 (N: 279, 142) 22.22 9.15
Week 12 (N: 279, 142) 30.11 12.68
Week 16 (N: 279, 142) 38.35 16.9
Week 20 (N: 279, 142) 43.01 15.49
Week 24 (N: 279, 142) 46.95 11.97
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 2.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0250
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 7.40
Confidence Interval (2-Sided) 95%
0.96 to 56.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 4.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0466
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.33
Confidence Interval (2-Sided) 95%
1.00 to 5.45
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept + Methotrexate, DMARD + Methotrexate
Comments Fisher's exact test was used to calculate the p-value. Statistical analysis presented above for Week 8.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments Statistical testing was done at alpha = 0.05 level, two-sided, without any adjustment for multiple comparisons.
Method Fisher Exact