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Study Comparing Etanercept in Combination With Methotrexate in Subjects With Rheumatoid Arthritis (PRESERVE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00565409
Recruitment Status : Completed
First Posted : November 30, 2007
Results First Posted : August 10, 2015
Last Update Posted : August 10, 2015
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Arthritis, Rheumatoid
Interventions Drug: Etanercept
Drug: Methotrexate
Drug: Placebo
Enrollment 834
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1 Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
Hide Arm/Group Description Participants received etanercept (ETN) 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks. Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) less than or equal to (≤) 3.2 at Week 36 and an average DAS28 less than or equal to (≤) 3.2 from Week 12 visit through Week 36. Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ 3.2 from Week 12 visit through Week 36. Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ 3.2 from Week 12 visit through Week 36.
Period Title: Period 1 Open Label
Started 834 0 0 0
Completed 756 0 0 0
Not Completed 78 0 0 0
Reason Not Completed
Adverse Event             17             0             0             0
Death             2             0             0             0
Lost to Follow-up             1             0             0             0
Other             21             0             0             0
Protocol Violation             14             0             0             0
Unsatisfactory Response-Efficacy             22             0             0             0
no conclusion of participation record             1             0             0             0
Period Title: After Period 1, Prior to Period 2
Started 756 0 0 0
Completed 604 0 0 0
Not Completed 152 0 0 0
Reason Not Completed
did not meet criteria             152             0             0             0
Period Title: Period 2 Double-Blind
Started 0 202 202 200
Completed 0 181 175 141
Not Completed 0 21 27 59
Reason Not Completed
Adverse Event             0             7             4             5
Death             0             2             0             0
Protocol Violation             0             4             6             2
Lost to Follow-up             0             0             1             0
Other             0             4             5             9
Unsatisfactory Response-Efficacy             0             4             11             43
Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
Hide Arm/Group Description Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
Overall Number of Baseline Participants 834
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 834 participants
48.36  (11.94)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 834 participants
Female
694
  83.2%
Male
140
  16.8%
1.Primary Outcome
Title Percentage of Participants Achieving 28 Joint Disease Activity Score (DAS28) Less Than or Equal to (≤) 3.2 at Week 88
Hide Description DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joint count (less than [<]20 percent [%] missing SJC or PJC was prorated), erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and Patient's General Health Visual Analog Scale (VAS). VAS is a line 0-100 millimeters (mm) in length; ranged from 0 (very well)-100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units equals (=) low disease activity.
Time Frame Week 88
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent to Treat population (mITT): all participants who took at least 1 dose of double-blind test article and had at least 1 post-randomization DAS28 evaluation
Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
Hide Arm/Group Description:
Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Overall Number of Participants Analyzed 201 201 197
Measure Type: Number
Unit of Measure: percentage of participants
82.6 79.1 42.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Sample size estimated based on moderate/severe rheumatoid arthritis(RA) trial. Study design included only moderate RA participants, thus a low disease activity estimate of 85% (ETN+MTX) vs 70% (MTX only) assumed, required 175 randomized participants in 3 treatments for a 90% power and Type I error of 0.05 to reject the null hypothesis of no ETN+MTX vs MTX only differences. More participants qualified for Period 2 than expected, Period 2 sample size roughly 15% larger than protocol-specified.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from Cochran-Mantel-Haenszel(CMH) test of general association, testing treatment effect on response. P-value and Odds Ratio (OR) stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments Loss of efficacy (LOE) imputation defined as LOE drop-outs were treated as non-responders/all other participants had LOCF applied as primary analysis.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.36
Confidence Interval (2-Sided) 95%
3.2 to 9.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3805
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments LOE imputation defined as LOE drop-outs were treated as non-responders and all other participants had LOCF applied as primary analysis.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.7 to 2.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments LOE imputation defined as LOE drop-outs were treated as non-responders and all other participants had LOCF applied as primary analysis.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.81
Confidence Interval (2-Sided) 95%
3.0 to 7.6
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Achieving DAS28 Low Disease Activity or Remission at Baseline, Weeks 4, 8, 12, 20, 28 and 36
Hide Description DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units = low disease activity, DAS28 < 2.6 units = remission.
Time Frame Baseline, Weeks 4, 8, 12, 20, 28, 36
Hide Outcome Measure Data
Hide Analysis Population Description
Period 1 Modified Intent to Treat population (P1 mITT): all participants who took at least 1 dose of open-label test article; N=number of participants with evaluable data; Last observation carried forward (LOCF)
Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
Hide Arm/Group Description:
Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
Overall Number of Participants Analyzed 829
Measure Type: Number
Unit of Measure: percentage of participants
Baseline-Low Disease Activity 0.36
Week 4-Low Disease Activity 35.98
Week 8-Low Disease Activity 49.57
Week 12-Low Disease Activity 61.75
Week 20-Low Disease Activity 69.25
Week 28-Low Disease Activity 75.79
Week 36-Low Disease Activity 81.96
Baseline-Remission 0
Week 4-Remission 16.52
Week 8-Remission 28.83
Week 12-Remission 38.73
Week 20-Remission 45.52
Week 28-Remission 54.24
Week 36-Remission 63.56
3.Secondary Outcome
Title Percentage of Participants Achieving DAS28 Low Disease Activity or Remission
Hide Description DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units = low disease activity, DAS28 < 2.6 units = remission.
Time Frame Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Hide Outcome Measure Data
Hide Analysis Population Description
Period 2 (P2) mITT
Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
Hide Arm/Group Description:
Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Overall Number of Participants Analyzed 201 201 197
Measure Type: Number
Unit of Measure: Percentage of participants
Week 36-Low Disease Activity 98.5 99.0 100.0
Week 40-Low Disease Activity 87.8 84.3 65.4
Week 48-Low Disease Activity 83.1 81.1 53.3
Week 56-Low Disease Activity 82.6 81.1 44.7
Week 64-Low Disease Activity 81.6 82.1 48.7
Week 72-Low Disease Activity 84.1 82.6 45.7
Week 80-Low Disease Activity 84.6 81.6 45.7
Week 88-Low Disease Activity 82.6 80.6 45.2
Week 36-Remission 81.1 79.6 80.2
Week 40-Remission 68.9 63.5 42.6
Week 48-Remission 65.7 62.7 36.5
Week 56-Remission 62.2 65.2 28.9
Week 64-Remission 63.7 61.2 30.5
Week 72-Remission 67.2 65.2 27.9
Week 80-Remission 67.2 64.7 29.9
Week 88-Remission 66.7 60.2 29.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 36 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0853
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.11
Confidence Interval (2-Sided) 95%
0.5 to 21.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 36 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8491
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.2 to 4.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 36 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1278
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.97
Confidence Interval (2-Sided) 95%
0.4 to 42.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 40 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.63
Confidence Interval (2-Sided) 95%
2.1 to 6.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 40 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3027
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.43
Confidence Interval (2-Sided) 95%
0.8 to 2.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 40 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.51
Confidence Interval (2-Sided) 95%
1.5 to 4.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 48 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.55
Confidence Interval (2-Sided) 95%
2.7 to 7.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 48 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5871
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.18
Confidence Interval (2-Sided) 95%
0.7 to 2.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 48 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.76
Confidence Interval (2-Sided) 95%
2.3 to 6.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 56 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.52
Confidence Interval (2-Sided) 95%
3.9 to 11.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 56 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6716
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.6 to 2.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 56 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.40
Confidence Interval (2-Sided) 95%
3.4 to 8.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 64 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.62
Confidence Interval (2-Sided) 95%
2.8 to 7.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 64 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9399
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.5 to 1.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 64 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.78
Confidence Interval (2-Sided) 95%
3.0 to 7.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 72 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.25
Confidence Interval (2-Sided) 95%
3.7 to 10.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 72 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6692
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.6 to 1.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 72 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.46
Confidence Interval (2-Sided) 95%
3.4 to 8.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 80 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.74
Confidence Interval (2-Sided) 95%
3.4 to 9.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 80 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4326
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.7 to 2.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 80 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.12
Confidence Interval (2-Sided) 95%
3.2 to 8.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 88 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.68
Confidence Interval (2-Sided) 95%
2.8 to 7.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 88 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6064
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.6 to 1.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 88 Low Disease Activity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.68
Confidence Interval (2-Sided) 95%
3.0 to 7.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 36 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4626
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.30
Confidence Interval (2-Sided) 95%
0.5 to 3.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 36 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2886
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.44
Confidence Interval (2-Sided) 95%
0.6 to 3.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 36 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7779
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.4 to 1.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 40 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.94
Confidence Interval (2-Sided) 95%
1.8 to 4.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 40 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2091
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.8 to 2.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 40 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.31
Confidence Interval (2-Sided) 95%
1.5 to 3.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 48 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.33
Confidence Interval (2-Sided) 95%
2.1 to 5.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 48 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5351
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.7 to 1.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 48 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.12
Confidence Interval (2-Sided) 95%
2.0 to 4.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 56 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.09
Confidence Interval (2-Sided) 95%
2.6 to 6.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 56 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4574
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.5 to 1.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 56 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.04
Confidence Interval (2-Sided) 95%
3.2 to 8.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 64 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.19
Confidence Interval (2-Sided) 95%
2.7 to 6.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 64 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5229
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.7 to 1.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 64 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.84
Confidence Interval (2-Sided) 95%
2.5 to 6.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 72 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.36
Confidence Interval (2-Sided) 95%
3.3 to 8.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 72 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6464
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.7 to 1.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 72 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.79
Confidence Interval (2-Sided) 95%
3.0 to 7.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 43
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 80 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.96
Confidence Interval (2-Sided) 95%
3.1 to 7.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 44
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 80 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5499
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.7 to 1.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 45
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 80 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.11
Confidence Interval (2-Sided) 95%
2.6 to 6.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 46
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 88 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.41
Confidence Interval (2-Sided) 95%
2.8 to 7.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 47
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 88 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1109
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.8 to 1.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 48
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 88 Remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from CMH test of general association, testing treatment effect on response. P-value and OR stratified by geographic region.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.85
Confidence Interval (2-Sided) 95%
2.5 to 6.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in DAS28 at Weeks 4, 8, 12, 20, 28 and 36
Hide Description The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (>5.1=high disease activity; <=3.2=low disease activity; <2.6=remission); a continuous variable which is a composite of 4 variables (the number of tender joints out of 28, the number of swollen joints out of 28 joints, erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PGA) of disease activity measured on a visual analogue scale (VAS) of 100 mm). Change equals (=) Week X observation minus (-) Baseline observation.
Time Frame Baseline, Weeks 4, 8, 12, 20, 28 and 36
Hide Outcome Measure Data
Hide Analysis Population Description
P1 mITT; Last observation carried forward (LOCF); N=Number of participants with evaluable data
Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
Hide Arm/Group Description:
Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
Overall Number of Participants Analyzed 829
Mean (Standard Error)
Unit of Measure: units on a scale
Baseline 4.37  (0.02)
Change at Week 4 -0.88  (0.03)
Change at Week 8 -1.22  (0.03)
Change at Week 12 -1.45  (0.03)
Change at Week 20 -1.60  (0.03)
Change at Week 28 -1.72  (0.04)
Change at Week 36 -1.89  (0.04)
5.Secondary Outcome
Title Change From Week 36 in DAS28 at Weeks 40, 48, 56, 64, 72, 80 and 88
Hide Description The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (>5.1=high disease activity; <=3.2=low disease activity; <2.6=remission); a continuous variable which is a composite of 4 variables (the number of tender joints out of 28, the number of swollen joints out of 28 joints, ESR mm/hour and PGA of disease activity measured on a VAS of 100 mm). Change = Week X observation - Week 36 observation.
Time Frame Weeks 36, 40, 48, 56, 64, 72, 80 and 88
Hide Outcome Measure Data
Hide Analysis Population Description
P2 mITT; LOCF; N=number of participants with evaluable data
Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
Hide Arm/Group Description:
Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Overall Number of Participants Analyzed 196 197 188
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Change at Week 40 0.30  (0.06) 0.31  (0.06) 0.84  (0.06)
Change at Week 48 0.40  (0.07) 0.36  (0.07) 1.25  (0.07)
Change at Week 56 0.44  (0.07) 0.37  (0.07) 1.35  (0.07)
Change at Week 64 0.47  (0.07) 0.40  (0.07) 1.33  (0.07)
Change at Week 72 0.35  (0.08) 0.38  (0.08) 1.40  (0.08)
Change at Week 80 0.40  (0.08) 0.40  (0.08) 1.42  (0.08)
Change at Week 88 0.39  (0.08) 0.50  (0.08) 1.44  (0.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 40
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.54
Confidence Interval (2-Sided) 95%
-0.7 to -0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 40
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9344
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.2 to 0.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 40
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.53
Confidence Interval (2-Sided) 95%
-0.7 to -0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.84
Confidence Interval (2-Sided) 95%
-1.0 to -0.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6173
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.1 to 0.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.89
Confidence Interval (2-Sided) 95%
-1.1 to -0.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.92
Confidence Interval (2-Sided) 95%
-1.1 to -0.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5136
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.1 to 0.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.98
Confidence Interval (2-Sided) 95%
-1.2 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 64
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.86
Confidence Interval (2-Sided) 95%
-1.1 to -0.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 64
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4868
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-0.1 to 0.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 64
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.93
Confidence Interval (2-Sided) 95%
-1.1 to -0.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 72
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.05
Confidence Interval (2-Sided) 95%
-1.3 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 72
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7847
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.2 to 0.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 72
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.02
Confidence Interval (2-Sided) 95%
-1.2 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 80
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.02
Confidence Interval (2-Sided) 95%
-1.2 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 80
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9810
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.2 to 0.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 80
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.02
Confidence Interval (2-Sided) 95%
-1.2 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 88
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.04
Confidence Interval (2-Sided) 95%
-1.3 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 88
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3562
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.3 to 0.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 88
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.94
Confidence Interval (2-Sided) 95%
-1.2 to -0.7
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to Loss of Low Disease Activity DAS28 and a Change of ≥ 0.6 Units in the DAS28
Hide Description DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. Low disease activity = DAS28 ≤ 3.2 units. DAS28 > 3.2 to 5.1 units = moderate to high disease activity.
Time Frame Week 36 up to Week 88
Hide Outcome Measure Data
Hide Analysis Population Description
P2 mITT;Imputation of failure; observed cases
Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
Hide Arm/Group Description:
Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Overall Number of Participants Analyzed 201 201 197
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(365.0 to NA)
NA [2] 
(NA to NA)
85.0
(82.0 to 135.0)
[1]
NA=not applicable, median and confidence interval not estimable due to small number of occurrences of event.
[2]
Median and confidence interval not estimable due to small number of occurrences of event.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Imputation of failure defined as participants who did not reach the endpoint and discontinued due to lack of efficacy, with reason of unsatisfactory response-efficacy, adverse event, other or protocol violation were set to an event at time of discontinuation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Week 88 censored data was censored at 372 days.
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Imputation of failure defined as participants who did not reach the endpoint and discontinued due to lack of efficacy, with reason of unsatisfactory response-efficacy, adverse event, other or protocol violation were set to an event at time of discontinuation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Week 88 censored data was censored at 372 days.
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Imputation of failure defined as participants who did not reach the endpoint and discontinued due to lack of efficacy, with reason of unsatisfactory response-efficacy, adverse event, other or protocol violation were set to an event at time of discontinuation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8622
Comments Week 88 censored data was censored at 372 days.
Method Log Rank
Comments [Not Specified]
7.Secondary Outcome
Title Time to Loss of Low Disease Activity DAS28
Hide Description DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR mm/hour and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 ≤ 3.2 units = low disease activity, DAS28 greater than (>)3.2 to 5.1 units = moderate to high disease activity.
Time Frame Week 36 up to Week 88
Hide Outcome Measure Data
Hide Analysis Population Description
P2 mITT;
Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
Hide Arm/Group Description:
Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Overall Number of Participants Analyzed 201 201 197
Median (95% Confidence Interval)
Unit of Measure: days
366.0 [1] 
(359.0 to NA)
NA [2] 
(358.0 to NA)
85.0
(81.0 to 134.0)
[1]
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event
[2]
Median and upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Week 88 censored data was censored at 372 days.
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9841
Comments Week 88 censored data was censored at 372 days.
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Week 88 censored data was censored at 372 days.
Method Log Rank
Comments [Not Specified]
8.Secondary Outcome
Title Proportion of Time Participants Had Low Disease Activity DAS28 Week 36 to Week 88
Hide Description DAS28 calculated from the number of SJC and PJC using the 28 joints, the ESR mm/hour and Patient's General Health VAS. VAS consisted of a line 0 to 100 mm in length; ranged from 0 (very well) to 100mm (extremely bad). Participants placed a mark indicating their health over the previous 2-3 weeks. Higher scores indicated greater affectation due to disease activity. DAS28 < 3.2 units = low disease activity. Cumulative proportion calculated as time-averaged Area Under the Curve (AUC) (AUC divided by number of weeks at that time point), with AUC calculated from Week 36 and Week 88.
Time Frame Week 36 up to Week 88
Hide Outcome Measure Data
Hide Analysis Population Description
P2 mITT; LOCF
Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
Hide Arm/Group Description:
Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Overall Number of Participants Analyzed 201 201 197
Mean (Standard Error)
Unit of Measure: proportion of weeks in DAS28 <3.2
0.85  (0.02) 0.84  (0.02) 0.58  (0.02)
9.Secondary Outcome
Title Change From Baseline in Prorated Swollen Joint Count at Weeks 4, 8, 12, 20, 28 and 36
Hide Description American College of Rheumatology (ACR), swollen joint count were an assessment of 28 joints. Joints are classified as either swollen or not swollen. If < 20% of swollen joints missing then total swollen joint prorated (multiplied by 28 divided by (/) number of non-missing swollen joints). Total possible score ranged from -28 to 28. An increase in swollen joints from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - baseline observation.
Time Frame Baseline, Weeks 4, 8, 12, 20, 28 and 36
Hide Outcome Measure Data
Hide Analysis Population Description
P1 mITT; N=number of participants with evaluable data; LOCF
Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
Hide Arm/Group Description:
Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
Overall Number of Participants Analyzed 830
Mean (Standard Error)
Unit of Measure: number of swollen joints
Baseline 3.82  (0.09)
Change at Week 4 -1.31  (0.08)
Change at Week 8 -1.96  (0.08)
Change at Week 12 -2.29  (0.08)
Change at Week 20 -2.60  (0.09)
Change at Week 28 -2.70  (0.09)
Change at Week 36 -2.67  (0.10)
10.Secondary Outcome
Title Prorated Swollen Joint Count at Week 36
Hide Description ACR, swollen joint count was an assessment of 28 joints. Joints were classified as either swollen or not swollen. If < 20% of swollen joints missing then total swollen joint prorated (multiplied by 28 divided by number of non-missing swollen joints). Total possible score of swollen joints ranged from 0-28.
Time Frame Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
P2 mITT; LOCF
Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
Hide Arm/Group Description:
Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Overall Number of Participants Analyzed 201 201 197
Mean (Standard Error)
Unit of Measure: number of swollen joints
0.63  (0.11) 0.57  (0.09) 0.59  (0.08)
11.Secondary Outcome
Title Change From Week 36 in Prorated Swollen Joint Count at Weeks 40, 48, 56, 64, 72, 80 and 88
Hide Description ACR, swollen joint count was an assessment of 28 joints. Joints were classified as either swollen or not swollen. If < 20% of swollen joints missing then total swollen joint prorated (multiplied by 28 divided by (/) number of non-missing swollen joints). Total possible score ranged from -28 to 28. An increase in swollen joints from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - Week 36 observation.
Time Frame Week 36, Weeks 40, 48, 56, 64, 72, 80 and 88
Hide Outcome Measure Data
Hide Analysis Population Description
P2 mITT; LOCF
Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
Hide Arm/Group Description:
Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Overall Number of Participants Analyzed 201 201 197
Least Squares Mean (Standard Error)
Unit of Measure: number of swollen joints
Change at Week 40 0.10  (0.11) 0.14  (0.11) 0.91  (0.11)
Change at Week 48 0.25  (0.15) 0.21  (0.15) 1.38  (0.15)
Change at Week 56 0.28  (0.16) 0.26  (0.16) 1.49  (0.16)
Change at Week 64 0.37  (0.17) 0.34  (0.17) 1.64  (0.17)
Change at Week 72 0.20  (0.16) 0.22  (0.16) 1.64  (0.17)
Change at Week 80 0.25  (0.18) 0.32  (0.18) 1.82  (0.18)
Change at Week 88 0.17  (0.18) 0.49  (0.18) 1.92  (0.18)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 40
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.81
Confidence Interval (2-Sided) 95%
-1.1 to -0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 40
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8015
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.3 to 0.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 40
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.78
Confidence Interval (2-Sided) 95%
-1.1 to -0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.14
Confidence Interval (2-Sided) 95%
-1.5 to -0.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8534
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.4 to 0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.18
Confidence Interval (2-Sided) 95%
-1.6 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.21
Confidence Interval (2-Sided) 95%
-1.7 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9074
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.4 to 0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.24
Confidence Interval (2-Sided) 95%
-1.7 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 64
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.28
Confidence Interval (2-Sided) 95%
-1.8 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 64
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9229
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.4 to 0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 64
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.30
Confidence Interval (2-Sided) 95%
-1.8 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 72
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.44
Confidence Interval (2-Sided) 95%
-1.9 to -1.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 72
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9279
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.5 to 0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 72
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.42
Confidence Interval (2-Sided) 95%
-1.9 to -1.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 80
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.58
Confidence Interval (2-Sided) 95%
-2.1 to -1.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 80
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7695
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.6 to 0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 80
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.50
Confidence Interval (2-Sided) 95%
-2.0 to -1.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 88
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.75
Confidence Interval (2-Sided) 95%
-2.3 to -1.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 88
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2182
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.8 to 0.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 88
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.44
Confidence Interval (2-Sided) 95%
-1.9 to -0.9
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in the Painful Joint Count at Weeks 4, 8, 12, 20, 28 and 36
Hide Description A total of 28 joints were assessed by the investigator using criteria based on pressure and joint manipulation. Total possible scores ranged from -28 to 28. An increase in joint pain count from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - Baseline observation.
Time Frame Baseline, Weeks 4, 8, 12, 20, 28 and 36
Hide Outcome Measure Data
Hide Analysis Population Description
P1 mITT; N=number of participants with evaluable data; LOCF
Arm/Group Title Etanercept 50 Milligrams (mg) Plus Methotrexate (MTX)-Period 1
Hide Arm/Group Description:
Participants received etanercept 50 mg subcutaneous (SC) injection plus oral MTX tablet 15 to 25 mg per week for 36 weeks.
Overall Number of Participants Analyzed 830
Mean (Standard Error)
Unit of Measure: number of painful joints
Baseline 5.09  (0.10)
Change at Week 4 -1.68  (0.10)
Change at Week 8 -2.50  (0.10)
Change at Week 12 -2.86  (0.11)
Change at Week 20 -3.11  (0.12)
Change at Week 28 -3.32  (0.12)
Change at Week 36 -3.51  (0.13)
13.Secondary Outcome
Title Painful Joint Count at Week 36
Hide Description A total of 28 joints were assessed by the investigator using criteria based on pressure and joint manipulation. Total possible score ranged form 0-28.
Time Frame Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
P2 mITT; LOCF
Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
Hide Arm/Group Description:
Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Overall Number of Participants Analyzed 201 201 197
Mean (Standard Error)
Unit of Measure: number of painful joints
0.64  (0.08) 0.69  (0.09) 0.74  (0.09)
14.Secondary Outcome
Title Change From Week 36 in Painful Joint Count at Weeks 40, 48, 56, 64, 72, 80 and 88
Hide Description Total of 28 joints were assessed by the investigator using criteria based on pressure and joint manipulation. Total possible scores ranged from -28 to 28. An increase in joint pain count from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression and a decrease represented improvement. Change = Week X observation - Week 36 observation.
Time Frame Weeks 36 40, 48, 56, 64, 72, 80 and 88
Hide Outcome Measure Data
Hide Analysis Population Description
P2 mITT; N=number of participants with evaluable data; LOCF
Arm/Group Title Etanercept 50 mg Plus MTX -Period 2 Etanercept 25 mg Plus MTX-Period 2 Placebo Plus MTX-Period 2
Hide Arm/Group Description:
Participants who were responders received etanercept 50 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with a 28 Joint Disease Activity Score (DAS28) ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received etanercept 25 mg SC injection plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Participants who were responders received matched placebo plus oral MTX (15 to 25 mg) tablet once per week for 52 weeks. Responders defined as participants with DAS28 ≤ 3.2 at Week 36 and an average DAS28 ≤ from Week 12 visit through Week 36.
Overall Number of Participants Analyzed 196 197 188
Least Squares Mean (Standard Error)
Unit of Measure: number of painful joints
Change at Week 40 0.61  (0.17) 0.49  (0.17) 1.47  (0.17)
Change at Week 48 0.67  (0.21) 0.63  (0.21) 2.69  (0.21)
Change at Week 56 0.61  (0.20) 0.66  (0.20) 2.67  (0.21)
Change at Week 64 0.79  (0.22) 0.73  (0.22) 2.76  (0.22)
Change at Week 72 0.63  (0.23) 0.78  (0.23) 3.01  (0.23)
Change at Week 80 0.74  (0.23) 0.88  (0.23) 3.02  (0.23)
Change at Week 88 0.73  (0.24) 0.78  (0.24) 3.14  (0.24)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 40
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.86
Confidence Interval (2-Sided) 95%
-1.3 to -0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 40
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6088
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
-0.3 to 0.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 40
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.98
Confidence Interval (2-Sided) 95%
-1.4 to -0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.02
Confidence Interval (2-Sided) 95%
-2.6 to -1.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9048
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.5 to 0.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.06
Confidence Interval (2-Sided) 95%
-2.6 to -1.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.06
Confidence Interval (2-Sided) 95%
-2.6 to -1.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8437
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.6 to 0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 56
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.00
Confidence Interval (2-Sided) 95%
-2.6 to -1.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 64
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.98
Confidence Interval (2-Sided) 95%
-2.6 to -1.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 64
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8587
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.6 to 0.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 64
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.03
Confidence Interval (2-Sided) 95%
-2.6 to -1.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 72
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.38
Confidence Interval (2-Sided) 95%
-3.0 to -1.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Etanercept 25 mg Plus MTX-Period 2
Comments Week 72
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6323
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.8 to 0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Etanercept 25 mg Plus MTX-Period 2, Placebo Plus MTX-Period 2
Comments Week 72
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.23
Confidence Interval (2-Sided) 95%
-2.9 to -1.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Etanercept 50 mg Plus MTX -Period 2, Placebo Plus MTX-Period 2
Comments Week 80
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments ANCOVA model: Change = Week 36 score + treatment + geographic region + DAS28 Strata. DAS28 Strata is defined as DAS28 low disease (≤3.2) or remission (<2.6) at randomization.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.28
Confidence Interval (2-Sided) 95%
-2.9 to -1.6
Estimation Comments [Not Specified]