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Study of Etanercept Monotherapy vs Methotrexate Monotherapy for Maintenance of Rheumatoid Arthritis Remission

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: NCT02373813
Recruitment Status : Completed
First Posted : February 27, 2015
Results First Posted : December 19, 2020
Last Update Posted : January 11, 2023
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: etanercept pre-filled syringe subcutaneous injection
Drug: Oral methotrexate
Drug: Placebo for etanercept subcutaneous injection
Drug: Placebo for methotrexate
Dietary Supplement: Folic acid (non-investigational product)
Enrollment 371
Recruitment Details This study was conducted at 97 centers in Canada, United States, Argentina, Bulgaria, Czech Republic, Spain, France, Germany, Greece, Hungary, Italy, Mexico, Poland, Portugal, and South Africa. The first participant enrolled on 20 February 2015; the last participant enrolled on 26 June 2018.
Pre-assignment Details After a 24-week open label run-in period, participants were randomly assigned in a 2:2:1 ratio to one of three treatment groups: methotrexate monotherapy, etanercept monotherapy, or etanercept plus methotrexate.
Arm/Group Title Open Label Run-In: Etanercept Plus Methotrexate Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 24 weeks. Participants also receive folic acid as standard of care.

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Period Title: Run-In Period
Started 371 0 0 0
Treated 368 0 0 0
Completed 255 [1] 0 0 0
Not Completed 116 0 0 0
Reason Not Completed
Other, Not Specified             5             0             0             0
Withdrawal by Subject             16             0             0             0
Decision by Sponsor             11             0             0             0
Protocol Violation             75             0             0             0
Lost to Follow-up             2             0             0             0
Adverse Event             3             0             0             0
Noncompliance             1             0             0             0
Ineligibility Determined             3             0             0             0
[1]
1 participant who completed the run-in period had no end of study case report form.
Period Title: Double-Blind Treatment Period
Started [1] 0 101 101 51
Received Investigational Product (IP) 0 101 100 51
Received Rescue Treatment 0 52 36 15
Completed 0 88 92 47
Not Completed 0 13 9 4
Reason Not Completed
Decision by Sponsor             0             1             2             0
Protocol Violation             0             2             0             0
Lost to Follow-up             0             0             1             1
Withdrawal by Subject             0             10             6             3
[1]
One participant who completed the run-in period was not randomized.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate Total
Hide Arm/Group Description

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Total of all reporting groups
Overall Number of Baseline Participants 101 101 51 253
Hide Baseline Analysis Population Description
Primary Analysis Set: All randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 101 participants 101 participants 51 participants 253 participants
56.2  (11.4) 54.8  (12.8) 55.9  (12.6) 55.6  (12.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 101 participants 51 participants 253 participants
Female
76
  75.2%
77
  76.2%
40
  78.4%
193
  76.3%
Male
25
  24.8%
24
  23.8%
11
  21.6%
60
  23.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 101 participants 51 participants 253 participants
Hispanic or Latino
13
  12.9%
19
  18.8%
8
  15.7%
40
  15.8%
Not Hispanic or Latino
88
  87.1%
82
  81.2%
43
  84.3%
213
  84.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 101 participants 51 participants 253 participants
American Indian or Alaska Native
4
   4.0%
3
   3.0%
2
   3.9%
9
   3.6%
Asian
2
   2.0%
0
   0.0%
1
   2.0%
3
   1.2%
Black
3
   3.0%
7
   6.9%
5
   9.8%
15
   5.9%
White
92
  91.1%
86
  85.1%
42
  82.4%
220
  87.0%
Other, Not Specified
0
   0.0%
5
   5.0%
1
   2.0%
6
   2.4%
1.Primary Outcome
Title Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission (≤ 3.3) at Week 48: Etanercept Monotherapy vs. Methotrexate Monotherapy
Hide Description The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Nonresponder imputation.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Overall Number of Participants Analyzed 101 101
Measure Type: Number
Unit of Measure: percentage of participants
28.7 49.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments The risk difference and its p-value were estimated from the chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 20.8
Confidence Interval (2-Sided) 95%
7.6 to 33.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.7
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With SDAI Remission (≤ 3.3) at Week 48: Etanercept and Methotrexate vs. Methotrexate Monotherapy
Hide Description The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Nonresponder imputation.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 101 51
Measure Type: Number
Unit of Measure: percentage of participants
28.7 52.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments The risk difference and its p-value were estimated from the chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 24.2
Confidence Interval (2-Sided) 95%
7.9 to 40.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.3
Estimation Comments [Not Specified]
3.Secondary Outcome
Title SDAI Score at All Measured Timepoints
Hide Description The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Observed cases at given timepoints.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 101 101 51
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 100 participants 101 participants 51 participants
1.29  (0.10) 1.26  (0.14) 1.18  (0.17)
Week 12 Number Analyzed 100 participants 100 participants 51 participants
7.01  (1.01) 4.37  (0.75) 4.39  (1.22)
Week 24 Number Analyzed 92 participants 96 participants 49 participants
5.61  (0.98) 4.98  (0.92) 3.28  (0.77)
Week 36 Number Analyzed 89 participants 93 participants 48 participants
4.03  (0.62) 2.25  (0.36) 2.41  (0.40)
Week 48 Number Analyzed 84 participants 90 participants 47 participants
3.41  (0.40) 2.33  (0.23) 2.86  (0.92)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.48 to 0.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.85
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.37 to 0.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.61
Confidence Interval (2-Sided) 95%
-5.89 to 0.67
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.037
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.64
Confidence Interval (2-Sided) 95%
-5.12 to -0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.063
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.33
Confidence Interval (2-Sided) 95%
-4.80 to 0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.46
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.64
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-3.27 to 2.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.031
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -1.62
Confidence Interval (2-Sided) 95%
-3.09 to -0.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -1.77
Confidence Interval (2-Sided) 95%
-3.20 to -0.35
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.71
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.55
Confidence Interval (2-Sided) 95%
-2.55 to 1.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.87
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -1.08
Confidence Interval (2-Sided) 95%
-1.99 to -0.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.45
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in SDAI Score at All Measured Timepoints
Hide Description The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3. A negative change from baseline indicates improvement.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Observed cases at given timepoint.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 101 101 51
Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 99 participants 100 participants 51 participants
5.67  (1.00) 3.14  (0.75) 3.21  (1.19)
Change at Week 24 Number Analyzed 91 participants 96 participants 49 participants
4.42  (0.98) 3.78  (0.91) 2.14  (0.78)
Change at Week 36 Number Analyzed 88 participants 93 participants 48 participants
2.90  (0.63) 1.06  (0.38) 1.30  (0.43)
Change at Week 48 Number Analyzed 83 participants 90 participants 47 participants
2.27  (0.39) 1.16  (0.24) 1.77  (0.94)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.46
Confidence Interval (2-Sided) 95%
-5.68 to 0.77
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.63
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.045
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.53
Confidence Interval (2-Sided) 95%
-4.99 to -0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.25
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.071
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.27
Confidence Interval (2-Sided) 95%
-4.75 to 0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.45
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.64
Confidence Interval (2-Sided) 95%
-3.28 to 2.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.037
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -1.61
Confidence Interval (2-Sided) 95%
-3.11 to -0.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.91
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -1.84
Confidence Interval (2-Sided) 95%
-3.30 to -0.39
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.62
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-2.54 to 1.53
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -1.12
Confidence Interval (2-Sided) 95%
-2.02 to -0.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.45
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Disease Activity Score (28 Joint) Calculated Using the Erythrocyte Sedimentation Rate Formula (DAS28-ESR) at All Measured Timepoints
Hide Description The DAS28-ESR is a modified composite index that was designed to measure disease activity using the number of tender and swollen joints based upon a 28-joint count, ESR in mm/hr, and a 100 mm VAS measuring the participant's general health, from 0 (best) to 100 (worst). DAS28-ESR scores range from 0 to 9.4, where higher scores represent higher disease activity.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Observed cases at given timepoint.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 101 101 51
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 100 participants 100 participants 51 participants
1.80  (0.06) 1.88  (0.07) 1.84  (0.09)
Week 12 Number Analyzed 99 participants 100 participants 51 participants
2.78  (0.14) 2.37  (0.12) 2.32  (0.16)
Week 24 Number Analyzed 92 participants 95 participants 49 participants
2.41  (0.13) 2.54  (0.14) 2.17  (0.12)
Week 36 Number Analyzed 87 participants 93 participants 48 participants
2.32  (0.11) 2.17  (0.08) 2.16  (0.12)
Week 48 Number Analyzed 85 participants 90 participants 47 participants
2.22  (0.10) 2.21  (0.08) 2.11  (0.13)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.75
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.19 to 0.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.43
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.11 to 0.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.049
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-0.91 to 0.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.23
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.032
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.77 to -0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.58 to 0.11
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
-0.24 to 0.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.35
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.51 to 0.18
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.41 to 0.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.44 to 0.21
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.92
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.26 to 0.24
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in DAS28-ESR at All Measured Timepoints
Hide Description The DAS28-ESR is a modified composite index that was designed to measure disease activity using the number of tender and swollen joints based upon a 28-joint count, ESR in mm/hr, and a 100 mm VAS measuring the participant's general health, from 0 (best) to 100 (worst). DAS28-ESR scores range from 0 to 9.4, where higher scores represent higher disease activity. A negative change from baseline indicates improvement.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Observed cases at given time point.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 101 101 51
Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 98 participants 100 participants 51 participants
0.96  (0.13) 0.50  (0.10) 0.48  (0.18)
Change at Week 24 Number Analyzed 91 participants 95 participants 49 participants
0.65  (0.12) 0.69  (0.13) 0.34  (0.11)
Change at Week 36 Number Analyzed 86 participants 92 participants 48 participants
0.53  (0.10) 0.31  (0.08) 0.35  (0.12)
Change at Week 48 Number Analyzed 84 participants 89 participants 47 participants
0.43  (0.09) 0.34  (0.07) 0.32  (0.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.032
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-0.91 to -0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-0.78 to -0.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.058
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.63 to 0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.29 to 0.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.27
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.49 to 0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-0.47 to 0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.43 to 0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.33 to 0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Disease Activity Score (28 Joint) Using the C-Reactive Protein Formula (DAS28-CRP) at All Measured Timepoints
Hide Description The DAS28-CRP is a composite index that was designed to measure disease activity using the number of tender and swollen joints based upon a 28-joint count, CRP in mg/L, and a 100 mm VAS measuring the participant's general health from 0 (best) to 100 (worst). DAS28-CRP scores range from 0 to 9.4, where higher scores represent higher disease activity.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Observed cases at given time point.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 101 101 51
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 100 participants 101 participants 51 participants
1.50  (0.03) 1.50  (0.04) 1.54  (0.05)
Week 12 Number Analyzed 100 participants 100 participants 51 participants
2.36  (0.13) 1.91  (0.09) 1.94  (0.15)
Week 24 Number Analyzed 92 participants 96 participants 49 participants
2.15  (0.11) 2.00  (0.11) 1.77  (0.09)
Week 36 Number Analyzed 89 participants 93 participants 48 participants
1.96  (0.09) 1.67  (0.06) 1.72  (0.08)
Week 48 Number Analyzed 84 participants 90 participants 47 participants
1.87  (0.07) 1.67  (0.05) 1.72  (0.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.60
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.09 to 0.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.97
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.10 to 0.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.41
Confidence Interval (2-Sided) 95%
-0.82 to -0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-0.76 to -0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.66 to -0.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.34
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.46 to 0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.47 to 0.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.49 to -0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.40 to -0.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-0.37 to -0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in DAS28-CRP at All Measured Timepoints
Hide Description The DAS28-CRP is a composite index that was designed to measure disease activity using the number of tender and swollen joints based upon a 28-joint count, CRP in mg/L, and a 100 mm VAS measuring the participant's general health from 0 (best) to 100 (worst). DAS28-CRP scores range from 0 to 9.4, where higher scores represent higher disease activity. A negative change from baseline indicates improvement.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Observed cases at given timepoint.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 101 101 51
Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 99 participants 100 participants 51 participants
0.84  (0.12) 0.42  (0.09) 0.41  (0.15)
Change at Week 24 Number Analyzed 91 participants 96 participants 49 participants
0.67  (0.11) 0.52  (0.11) 0.25  (0.08)
Change at Week 36 Number Analyzed 88 participants 93 participants 48 participants
0.49  (0.09) 0.18  (0.06) 0.20  (0.08)
Change at Week 48 Number Analyzed 83 participants 90 participants 47 participants
0.40  (0.07) 0.19  (0.04) 0.21  (0.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.43
Confidence Interval (2-Sided) 95%
-0.82 to -0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.72 to -0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.15
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.69 to -0.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.34
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.46 to 0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.52 to -0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.51 to -0.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.43 to 0.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.37 to -0.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Clinical Disease Activity Index (CDAI) at All Measured Timepoints
Hide Description The CDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, and Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable. The CDAI score ranges from 0 to 76, where a higher score represents worse disease.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Observed cases at given timepoint.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 101 101 51
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 101 participants 101 participants 51 participants
1.01  (0.10) 0.92  (0.13) 0.71  (0.12)
Week 12 Number Analyzed 100 participants 101 participants 51 participants
6.42  (0.98) 4.08  (0.74) 3.95  (1.20)
Week 24 Number Analyzed 92 participants 96 participants 49 participants
5.07  (0.95) 4.63  (0.91) 2.35  (0.60)
Week 36 Number Analyzed 89 participants 93 participants 48 participants
3.60  (0.63) 1.93  (0.36) 2.04  (0.41)
Week 48 Number Analyzed 85 participants 92 participants 47 participants
3.06  (0.38) 2.00  (0.23) 2.61  (0.91)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.067
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.62 to 0.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.59
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.41 to 0.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.46
Confidence Interval 95%
-5.66 to 0.74
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.62
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.059
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.34
Confidence Interval (2-Sided) 95%
-4.76 to 0.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.23
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.72
Confidence Interval (2-Sided) 95%
-4.95 to -0.50
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.38
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.74
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-3.04 to 2.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.039
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -1.56
Confidence Interval (2-Sided) 95%
-3.03 to -0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -1.66
Confidence Interval (2-Sided) 95%
-3.10 to -0.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-2.43 to 1.52
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.85
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -1.07
Confidence Interval (2-Sided) 95%
-1.94 to -0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.44
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in CDAI at All Measured Timepoints
Hide Description The CDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, and Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable. The CDAI score ranges from 0 to 76, where a higher score represents worse disease. A negative change from baseline indicates improvement.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Observed cases at given timepoint.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 101 101 51
Mean (Standard Error)
Unit of Measure: score on a scale
Change at Week 12 Number Analyzed 100 participants 101 participants 51 participants
5.39  (0.97) 3.15  (0.73) 3.24  (1.17)
Change at Week 24 Number Analyzed 92 participants 96 participants 49 participants
4.09  (0.95) 3.75  (0.90) 1.70  (0.61)
Change at Week 36 Number Analyzed 89 participants 93 participants 48 participants
2.69  (0.63) 1.07  (0.37) 1.41  (0.40)
Change at Week 48 Number Analyzed 85 participants 92 participants 47 participants
2.17  (0.37) 1.15  (0.23) 2.00  (0.92)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.15
Confidence Interval 95%
-5.29 to 1.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.59
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.067
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.24
Confidence Interval (2-Sided) 95%
-4.63 to 0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.40
Confidence Interval (2-Sided) 95%
-4.62 to -0.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.79
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-2.91 to 2.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.30
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.090
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -1.27
Confidence Interval (2-Sided) 95%
-2.75 to 0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.91
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -1.61
Confidence Interval (2-Sided) 95%
-3.06 to -0.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.86
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-2.15 to 1.81
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.84
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments [Not Specified]
Method two sample t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -1.02
Confidence Interval (2-Sided) 95%
-1.88 to -0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.43
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percentage of Participants With SDAI Remission (≤ 3.3) at All Measured Timepoints
Hide Description The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Observed cases at given time point.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 101 101 51
Measure Type: Number
Unit of Measure: percentage of participants
Baseline Number Analyzed 100 participants 101 participants 51 participants
96.0 92.1 96.1
Week 12 Number Analyzed 100 participants 100 participants 51 participants
50.0 64.0 74.5
Week 24 Number Analyzed 98 participants 99 participants 50 participants
38.8 56.6 62.0
Week 36 Number Analyzed 97 participants 99 participants 49 participants
36.1 55.6 55.1
Week 48 Number Analyzed 95 participants 96 participants 48 participants
30.5 52.1 56.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-6.5 to 6.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.38
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -3.9
Confidence Interval (2-Sided) 95%
-10.4 to 2.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 24.5
Confidence Interval (2-Sided) 95%
9.0 to 40.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.063
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 14.0
Confidence Interval (2-Sided) 95%
0.4 to 27.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 23.2
Confidence Interval (2-Sided) 95%
6.7 to 39.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 17.8
Confidence Interval (2-Sided) 95%
4.1 to 31.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 19.0
Confidence Interval (2-Sided) 95%
2.1 to 35.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 19.5
Confidence Interval (2-Sided) 95%
5.8 to 33.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 25.7
Confidence Interval (2-Sided) 95%
8.9 to 42.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 21.6
Confidence Interval (2-Sided) 95%
7.9 to 35.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.0
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants With Boolean Remission at All Measured Timepoints
Hide Description

A participant achieves Boolean remission (66/68-joint count) if all of the following criteria are met at a single timepoint:

  • 68-joint tender joint count ≤ 1
  • 66-joint swollen joint count ≤ 1
  • CRP (mg/dL) ≤ 1
  • Patient's Global Assessment of Disease Activity using a VAS (where 0=no arthritis activity at all and 10=worst arthritis activity imaginable) ≤ 1.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Observed cases at given timepoint.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 101 101 51
Measure Type: Number
Unit of Measure: percentage of participants
Baseline Number Analyzed 100 participants 101 participants 51 participants
34.0 34.7 45.1
Week 12 Number Analyzed 100 participants 100 participants 51 participants
18.0 23.0 19.6
Week 24 Number Analyzed 92 participants 96 participants 49 participants
15.2 16.7 26.5
Week 36 Number Analyzed 89 participants 93 participants 48 participants
14.6 20.4 27.1
Week 48 Number Analyzed 84 participants 90 participants 47 participants
20.2 13.3 25.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 11.1
Confidence Interval (2-Sided) 95%
-5.4 to 27.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-12.5 to 13.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.98
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 1.6
Confidence Interval (2-Sided) 95%
-11.6 to 14.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 5.0
Confidence Interval (2-Sided) 95%
-6.2 to 16.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 11.3
Confidence Interval (2-Sided) 95%
-3.1 to 25.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-9.0 to 11.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 12.5
Confidence Interval (2-Sided) 95%
-2.1 to 27.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 5.8
Confidence Interval (2-Sided) 95%
-5.2 to 16.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 5.3
Confidence Interval (2-Sided) 95%
-9.8 to 20.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments The risk difference and its p-value were estimated from the Chi-squared test with continuity correction.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -6.9
Confidence Interval (2-Sided) 95%
-18.0 to 4.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.7
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Percentage of Participants With Disease Worsening
Hide Description

Percentage of participants who fulfilled disease-worsening criteria for the first time is presented. Disease worsening is defined as any of the following:

  • an SDAI > 3.3 and ≤ 11 during 2 consecutive visits at least 2 weeks apart
  • SDAI > 3.3 and ≤ 11 on 3 or more separate visits
  • SDAI > 11 after randomization.

The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.

Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Observed cases at given timepoint.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 101 101 51
Measure Type: Number
Unit of Measure: percentage of participants
Baseline Number Analyzed 100 participants 101 participants 51 participants
0.0 0.0 0.0
Week 12 Number Analyzed 100 participants 100 participants 51 participants
42.0 23.0 17.6
Week 24 Number Analyzed 92 participants 96 participants 49 participants
8.7 14.6 6.1
Week 36 Number Analyzed 89 participants 93 participants 48 participants
10.1 3.2 8.3
Week 48 Number Analyzed 84 participants 90 participants 47 participants
4.8 0.0 4.3
14.Secondary Outcome
Title Time to Disease Worsening
Hide Description

Disease worsening is defined as any of the following:

  • an SDAI > 3.3 and ≤ 11 during 2 consecutive visits at least 2 weeks apart
  • SDAI > 3.3 and ≤ 11 on 3 or more separate visits
  • SDAI > 11 after randomization.

The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.

Time Frame up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: all randomized participants. Participants with disease worsening.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 63 40 18
Median (Full Range)
Unit of Measure: weeks
12.14
(2.3 to 48.7)
13.21
(3.0 to 36.1)
18.93
(7.0 to 48.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments P-value was based on the Log-rank test for overall difference on disease-worsening event between two groups.
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments P-value was based on the Log-rank test for overall difference on disease-worsening event between two groups.
Method Log Rank
Comments [Not Specified]
15.Secondary Outcome
Title Time to Recapture SDAI Remission After Starting Rescue Treatment
Hide Description

In participants who receive rescue treatment during the double-blind treatment period.

The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.

Time Frame Between rescue and remission or Week 48, whichever comes first.
Hide Outcome Measure Data
Hide Analysis Population Description
Rescue Analysis Set: randomized participants who met the definition of disease-worsening and received both at least 1 dose of active rescue therapy etanercept and at least 1 dose of active rescue therapy methotrexate. Participants who recaptured SDAI remission. Observed cases.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate
Hide Arm/Group Description:

Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus placebo to methotrexate for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening initiated rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).

Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care.

After randomization, a participant experiencing protocol-defined disease worsening continued on the assigned treatments (as rescue treatment).

Overall Number of Participants Analyzed 37 27 12
Median (Full Range)
Unit of Measure: weeks
11.00
(0.6 to 41.1)
12.00
(6.0 to 32.0)
11.36
(6.0 to 35.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Plus Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments P-value was based on the Log-rank test for overall difference on disease-worsening event between two groups.
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-Blind Treatment: Methotrexate Monotherapy, Double-Blind Treatment: Etanercept Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments P-value was based on the Log-rank test for overall difference on disease-worsening event between two groups.
Method Log Rank
Comments [Not Specified]
16.Secondary Outcome
Title Percentage of Participants Receiving Rescue Treatment Who Experienced SDAI Remission at Week 48
Hide Description The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Rescue Analysis Set: randomized participants who met the definition of disease-worsening and received both at least 1 dose of active rescue therapy etanercept and at least 1 dose of active rescue therapy methotrexate. Observed cases.
Arm/Group Title Double-Blind Treatment: Methotrexate Monotherapy Double-Blind Treatment: Etanercept Monotherapy Double-Blind Treatment: Etanercept Plus Methotrexate