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Etanercept and Methotrexate in Combination or as Monotherapy in Psoriatic Arthritis

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: NCT02376790
Recruitment Status : Completed
First Posted : March 3, 2015
Results First Posted : February 22, 2019
Last Update Posted : March 6, 2019
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 Psoriatic Arthritis
Interventions Drug: Etanercept
Drug: Methotrexate
Drug: Placebo to Etanercept
Drug: Placebo to Methotrexate
Enrollment 851
Recruitment Details This study was conducted at 124 centers in Europe, Latin America, North America, and South Africa. Participants were enrolled from 03 March 2015 to 07 July 2017.
Pre-assignment Details

The study consisted of a 30-day screening period, a 48-week randomized double blind treatment period, and a 30-day safety follow-up period.

Participants were randomly assigned in a 1:1:1 ratio to 1 of 3 treatment groups.

Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks. Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks. Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Period Title: Overall Study
Started 284 284 283
Received Treatment 282 284 282
Completed 224 237 230
Not Completed 60 47 53
Reason Not Completed
Withdrawal by Subject             43             36             37
Decision by Sponsor             2             1             4
Lost to Follow-up             15             10             12
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate Total
Hide Arm/Group Description Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks. Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks. Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks. Total of all reporting groups
Overall Number of Baseline Participants 284 284 283 851
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 284 participants 284 participants 283 participants 851 participants
48.7  (13.1) 48.5  (13.5) 48.1  (12.7) 48.4  (13.1)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 284 participants 284 participants 283 participants 851 participants
≤ 65 years
257
  90.5%
251
  88.4%
259
  91.5%
767
  90.1%
> 65 years
27
   9.5%
33
  11.6%
24
   8.5%
84
   9.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 284 participants 284 participants 283 participants 851 participants
Female
160
  56.3%
133
  46.8%
139
  49.1%
432
  50.8%
Male
124
  43.7%
151
  53.2%
144
  50.9%
419
  49.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 284 participants 284 participants 283 participants 851 participants
Hispanic or Latino
58
  20.4%
70
  24.6%
69
  24.4%
197
  23.1%
Not Hispanic or Latino
226
  79.6%
214
  75.4%
214
  75.6%
654
  76.9%
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 284 participants 284 participants 283 participants 851 participants
American Indian or Alaska Native
11
   3.9%
11
   3.9%
8
   2.8%
30
   3.5%
Asian
3
   1.1%
1
   0.4%
1
   0.4%
5
   0.6%
Black (or African American)
4
   1.4%
0
   0.0%
3
   1.1%
7
   0.8%
Mixed Race
0
   0.0%
1
   0.4%
0
   0.0%
1
   0.1%
Native Hawaiian or Other Pacific Islander
1
   0.4%
1
   0.4%
0
   0.0%
2
   0.2%
Other
10
   3.5%
18
   6.3%
6
   2.1%
34
   4.0%
White
255
  89.8%
252
  88.7%
265
  93.6%
772
  90.7%
Body Mass Index (BMI)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 284 participants 283 participants 283 participants 850 participants
≤ 30 kg/m²
146
  51.4%
153
  54.1%
160
  56.5%
459
  54.0%
> 30 kg/m²
138
  48.6%
130
  45.9%
123
  43.5%
391
  46.0%
[1]
Measure Analysis Population Description: Participants with available data
Prior Use of Non-biologic Disease Modifying Antirheumatic Drugs (DMARDs)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 284 participants 284 participants 283 participants 851 participants
Yes
38
  13.4%
26
   9.2%
43
  15.2%
107
  12.6%
No
246
  86.6%
258
  90.8%
240
  84.8%
744
  87.4%
Duration of Psoriatic Arthritis Disease   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 231 participants 222 participants 231 participants 684 participants
3.64  (6.85) 3.10  (5.96) 2.96  (5.99) 3.24  (6.28)
[1]
Measure Analysis Population Description: Participants with available data
Swollen Joint Count   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Joints
Number Analyzed 284 participants 283 participants 282 participants 849 participants
12.9  (9.9) 11.5  (9.6) 11.2  (9.1) 11.9  (9.6)
[1]
Measure Description: A total of 66 joints were scored for presence or absence of swelling.
[2]
Measure Analysis Population Description: Participants with available data
Tender Joint Count   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Joints
Number Analyzed 284 participants 283 participants 282 participants 849 participants
20.9  (15.0) 18.8  (14.5) 20.0  (15.3) 19.9  (14.9)
[1]
Measure Description: A total of 68 joints were scored for presence or absence of tenderness.
[2]
Measure Analysis Population Description: Participants with available data
Physician Global Assessment of Disease Activity   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 284 participants 284 participants 282 participants 850 participants
58.6  (19.4) 58.3  (18.2) 58.0  (17.8) 58.3  (18.5)
[1]
Measure Description: Assessed by the physician on a 100 mm visual analog scale (VAS), where 0 mm = No activity at all and 100 mm = Worst activity imaginable.
[2]
Measure Analysis Population Description: Participants with available data
Patient Global Assessment of Disease Activity   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 283 participants 284 participants 282 participants 849 participants
60.7  (22.5) 62.9  (22.1) 61.0  (20.8) 61.5  (21.8)
[1]
Measure Description: Assessed by the participant on a 100 mm VAS, where 0 mm = No arthritis activity at all and 100 mm = Worst arthritis activity imaginable.
[2]
Measure Analysis Population Description: Participants with available data
Patient Global Assessment of Joint Pain   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 283 participants 284 participants 282 participants 849 participants
56.1  (21.7) 56.5  (22.3) 55.7  (21.6) 56.1  (21.8)
[1]
Measure Description: Participants assessed their joint pain on a 100 mm VAS, where 0 mm = No pain at all and 100 mm = Worst pain imaginable.
[2]
Measure Analysis Population Description: Participants with available data
Disability Index of the Health Assessment Questionnaire (HAQ-DI)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 283 participants 284 participants 282 participants 849 participants
1.3  (0.6) 1.1  (0.6) 1.2  (0.6) 1.2  (0.6)
[1]
Measure Description: The HAQ-DI is a patient-reported questionnaire consisting of 20 questions in eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability.
[2]
Measure Analysis Population Description: Participants with available data
C-reactive Protein (CRP) Concentration   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  mg/L
Number Analyzed 284 participants 282 participants 283 participants 849 participants
10.52  (16.29) 10.72  (15.59) 8.70  (11.65) 9.98  (14.66)
[1]
Measure Description: C-reactive protein (CRP) is a protein found in blood. CRP levels rise in response to inflammation.
[2]
Measure Analysis Population Description: Participants with available data
Psoriatic Arthritis Disease Activity Score (PASDAS)   [1] [2] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 282 participants 279 participants 280 participants 841 participants
6.10
(2.2 to 9.1)
6.02
(2.5 to 10.2)
5.95
(3.0 to 9.4)
6.02
(2.2 to 10.2)
[1]
Measure Description:

PASDAS is a measure of disease activity derived from the following:

  • Physician and patient global assessment of disease activity (0-100 VAS)
  • 68 tender joint count
  • 66 swollen joint count
  • Short Form-36 Questionnaire (SF-36) physical component summary (general health status on a scale from 0-100)
  • Tender dactylitis count (each digit assessed for tender dactylitis; total score 0-20)
  • Leeds enthesitis index (enthesitis assessed at 6 sites; total score of 0-6)
  • CRP

The composite score is a weighted index where higher scores indicate more severe disease.

[2]
Measure Analysis Population Description: Participants with available data
Clinical Disease Activity Index (CDAI)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 283 participants 283 participants 281 participants 847 participants
30.51  (13.26) 28.45  (12.89) 28.55  (12.71) 29.17  (12.98)
[1]
Measure Description:

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the following items:

  • 28 tender joint count,
  • 28 swollen joint count,
  • Patient's Global Assessment of Disease Activity measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest;
  • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest.

The CDAI score ranges from 0-76 where lower scores indicate less disease activity.

[2]
Measure Analysis Population Description: Participants with available data
Simplified Disease Activity Index (SDAI)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 283 participants 281 participants 281 participants 845 participants
31.56  (13.52) 29.52  (13.19) 29.43  (12.90) 30.17  (13.23)
[1]
Measure Description:

The Simplified Disease Activity Index (SDAI) is a composite index that is calculated as the sum of the following items:

  • 28 tender joint count,
  • 28 swollen joint count,
  • Patient's Global Assessment of Disease Activity measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest;
  • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest.
  • CRP

The SDAI score ranges from 0 to 86 with higher scores representing worse disease.

[2]
Measure Analysis Population Description: Participants with available data
Disease Activity Score 28 (DAS28)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 283 participants 281 participants 281 participants 845 participants
4.93  (1.11) 4.80  (1.13) 4.75  (1.12) 4.83  (1.12)
[1]
Measure Description:

The DAS28 measures the severity of disease at a specific time and is derived from the following variables:

  • 28 tender joint count
  • 28 swollen joint count
  • C-reactive protein (CRP) concentration
  • Patient's global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.

DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. Higher scores indicate higher disease activity.

[2]
Measure Analysis Population Description: Participants with available data
Medical Outcomes Health Survey Short Form 36 Items Version 2 (SF-36 v2)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
PCS Number Analyzed 282 participants 284 participants 282 participants 848 participants
35.587  (8.411) 37.835  (8.381) 37.353  (9.243) 36.927  (8.730)
MCS Number Analyzed 282 participants 284 participants 282 participants 848 participants
45.174  (12.073) 45.107  (12.496) 46.256  (11.236) 45.511  (11.946)
[1]
Measure Description: The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains. Two summary component scores are calculated: mental component summary score (MCS) and physical component summary score (PCS). Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning.
[2]
Measure Analysis Population Description: Participants with available data
Leeds Dactylitis Index (LDI)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 284 participants 283 participants 282 participants 849 participants
56.89  (174.56) 50.07  (137.20) 44.11  (143.17) 50.37  (152.47)
[1]
Measure Description: The Leeds Dactylitis Index quantitatively measures dactylitis using the circumference of involved digits and control digits and tenderness of involved digits (on a scale from 0-3). The control digit is either the contralateral digit (digit on opposite hand or foot), or if the contralateral digit is also affected, from a standard reference table. The ratio of circumference between an affected digit and the control digit is multiplied by the tenderness score for the affected digit. The results from each involved digit are summed to provide the final LDI. A higher LDI indicates worse dactylitis.
[2]
Measure Analysis Population Description: Participants with available data
Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 284 participants 283 participants 282 participants 849 participants
3.9  (4.3) 3.7  (4.3) 4.1  (4.5) 3.9  (4.4)
[1]
Measure Description: The SPARCC enthesitis index assesses enthesitis at 18 sites for palpitation with a resultant total score of 0 to 16 (for scoring purposes, the inferior patella and tibial tuberosity are considered 1 site because of their anatomical proximity). Tenderness at each site is quantified on a dichotomous basis (0 = non-tender, 1 = tender). A higher count represents greater enthesitis burden.
[2]
Measure Analysis Population Description: Participants with available data
Percentage of Body Surface Area (BSA) Involved in Psoriasis   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Percent body surface area
Number Analyzed 284 participants 284 participants 283 participants 851 participants
12.68  (18.78) 10.76  (14.66) 10.74  (15.58) 11.40  (16.44)
[1]
Measure Description: The physician’s assessment of the percentage of the participant’s total body surface area involved with psoriasis.
[2]
Measure Analysis Population Description: Participants with available data
Static Physician Global Assessment (sPGA)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 281 participants 284 participants 283 participants 848 participants
2.6  (1.1) 2.6  (1.0) 2.5  (1.0) 2.6  (1.0)
[1]
Measure Description:

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician’s global assessment of the participant’s psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

  1. = almost clear
  2. = mild
  3. = moderate
  4. = marked
  5. = severe
[2]
Measure Analysis Population Description: Participants with available data
1.Primary Outcome
Title Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 24
Hide Description

A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met:

  • ≥ 20% improvement in 68 tender joint count;
  • ≥ 20% improvement in 66 swollen joint count; and
  • ≥ 20% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • C-reactive protein concentration.
Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; missing postbaseline data were imputed using non-responder imputation.
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Measure Type: Number
Unit of Measure: percentage of participants
50.7 60.9 65.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments The primary hypothesis of this study is that etanercept plus methotrexate therapy and etanercept monotherapy are more efficacious than methotrexate monotherapy as measured by the percentage of participants with psoriatic arthritis achieving ACR 20 response at week 24.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments Adjusted p-value was obtained by applying a Bonferroni-based testing procedure for multiplicity adjustment to control the family-wise, two-sided type one error rate at 0.05.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 13.9
Confidence Interval (2-Sided) 95%
5.8 to 22.0
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments The primary hypothesis of this study is that etanercept plus methotrexate therapy and etanercept monotherapy are more efficacious than methotrexate monotherapy as measured by the percentage of participants with psoriatic arthritis achieving ACR 20 response at week 24.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments Adjusted p-value was obtained by applying a Bonferroni-based testing procedure for multiplicity adjustment to control the family-wise, two-sided type one error rate at 0.05.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 9.2
Confidence Interval (2-Sided) 95%
1.0 to 17.3
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
2.Secondary Outcome
Title Percentage of Participants With a Minimal Disease Activity (MDA) Response at Week 24
Hide Description

Minimal Disease Activity (MDA) is a measure of low disease activity specific for psoriatic arthritis (PsA) that incorporates measures of joint and entheseal inflammation, skin disease, patient reported outcomes and functional disability to assess disease activity. Participants were classified as achieving MDA if they fulfilled 5 of the following 7 outcome measures:

  • Tender joint count (0-68) ≤ 1
  • Swollen joint count (0-66) ≤ 1
  • Body surface area (BSA) involvement with psoriasis (0% to 100%) ≤ 3%
  • Patient global assessment of joint pain VAS (0-100) ≤ 15
  • Patient global assessment of disease activity VAS (0-100) ≤ 20
  • HAQ-DI (0-3) ≤ 0.5
  • Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index (18 sites assessed for enthesitis with an overall score of 0 - 16) ≤ 1
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; missing postbaseline data were imputed using non-responder imputation.
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Measure Type: Number
Unit of Measure: percentage of participants
22.9 35.9 35.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments The secondary hypothesis of this study was that etanercept plus methotrexate therapy and etanercept monotherapy are more efficacious than methotrexate monotherapy as measured by the percentage of participants with PsA achieving MDA response at week 24.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments Adjusted p-value was obtained by applying a Bonferroni-based testing procedure for multiplicity adjustment to control the family-wise, two-sided type one error rate at 0.05.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 12.2
Confidence Interval (2-Sided) 95%
4.9 to 19.6
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments The secondary hypothesis of this study was that etanercept plus methotrexate therapy and etanercept monotherapy are more efficacious than methotrexate monotherapy as measured by the percentage of participants with PsA achieving MDA response at week 24.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments Adjusted p-value was obtained by applying a Bonferroni-based testing procedure for multiplicity adjustment to control the family-wise, two-sided type one error rate at 0.05.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 11.6
Confidence Interval (2-Sided) 95%
4.2 to 18.9
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
3.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response Over Time
Hide Description

A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met:

  • ≥ 20% improvement in 68 tender joint count;
  • ≥ 20% improvement in 66 swollen joint count; and
  • ≥ 20% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • C-reactive protein.
Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point.
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Measure Type: Number
Unit of Measure: percentage of participants
Week 4 Number Analyzed 280 participants 280 participants 276 participants
25.0 44.3 46.4
Week 8 Number Analyzed 271 participants 274 participants 268 participants
46.5 60.2 60.8
Week 12 Number Analyzed 267 participants 267 participants 263 participants
46.8 65.5 70.3
Week 16 Number Analyzed 253 participants 256 participants 248 participants
58.5 69.5 71.8
Week 24 Number Analyzed 253 participants 256 participants 256 participants
56.9 67.6 71.9
Week 36 Number Analyzed 243 participants 248 participants 240 participants
66.3 77.0 74.2
Week 48 Number Analyzed 229 participants 237 participants 230 participants
70.7 83.1 80.4
4.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response Over Time
Hide Description

A positive ACR50 response is defined if the following 3 criteria for improvement from baseline were met:

  • ≥ 50% improvement in 68 tender joint count;
  • ≥ 50% improvement in 66 swollen joint count; and
  • ≥ 50% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • C-reactive protein.
Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Measure Type: Number
Unit of Measure: percentage of participants
Week 4 Number Analyzed 281 participants 279 participants 276 participants
6.0 16.5 18.8
Week 8 Number Analyzed 272 participants 275 participants 269 participants
15.1 31.3 30.1
Week 12 Number Analyzed 267 participants 267 participants 263 participants
16.9 40.4 39.2
Week 16 Number Analyzed 253 participants 256 participants 251 participants
29.2 43.8 43.4
Week 24 Number Analyzed 252 participants 257 participants 256 participants
30.6 44.4 45.7
Week 36 Number Analyzed 244 participants 246 participants 241 participants
41.8 57.3 56.0
Week 48 Number Analyzed 229 participants 238 participants 231 participants
49.3 63.0 60.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments Analysis of the percentage of participants with an ACR50 response at week 24.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is unadjusted and considered descriptive.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 14.7
Confidence Interval (2-Sided) 95%
6.4 to 23.0
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments Analysis of the percentage of participants with an ACR50 response at week 24.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments P-value is unadjusted and considered descriptive.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 11.8
Confidence Interval (2-Sided) 95%
3.4 to 20.2
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
5.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response Over Time
Hide Description

A positive ACR70 response is defined if the following 3 criteria for improvement from baseline were met:

  • ≥ 70% improvement in 68 tender joint count;
  • ≥ 70% improvement in 66 swollen joint count; and
  • ≥ 70% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • C-reactive protein.
Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point.
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Measure Type: Number
Unit of Measure: percentage of participants
Week 4 Number Analyzed 281 participants 280 participants 276 participants
2.8 3.6 5.1
Week 8 Number Analyzed 272 participants 277 participants 269 participants
4.4 15.2 14.5
Week 12 Number Analyzed 267 participants 268 participants 264 participants
5.2 24.3 22.3
Week 16 Number Analyzed 252 participants 256 participants 251 participants
10.7 24.2 25.5
Week 24 Number Analyzed 253 participants 257 participants 256 participants
13.8 29.2 27.7
Week 36 Number Analyzed 245 participants 247 participants 242 participants
19.6 38.5 33.5
Week 48 Number Analyzed 230 participants 237 participants 232 participants
25.2 39.7 39.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments Analysis of the percentage of participants with an ACR70 response at week 24.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is unadjusted and considered descriptive.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 13.4
Confidence Interval (2-Sided) 95%
6.5 to 20.4
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments Analysis of the percentage of participants with an ACR70 response at week 24.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is unadjusted and considered descriptive.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 13.7
Confidence Interval (2-Sided) 95%
6.7 to 20.7
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
6.Secondary Outcome
Title Change From Baseline in Tender Joint Count Over Time
Hide Description The tender joint count is an assessment of the pain and/or tenderness of 68 joints using a 0 to 1 point scale (0 = none, 1 = present). The total tender joint count is calculated by summing the number of joints with present tenderness.
Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Mean (Standard Error)
Unit of Measure: tender joints
Week 4 Number Analyzed 280 participants 279 participants 277 participants
-5.7  (0.6) -6.4  (0.6) -7.4  (0.6)
Week 8 Number Analyzed 271 participants 276 participants 269 participants
-7.8  (0.7) -8.9  (0.6) -9.4  (0.7)
Week 12 Number Analyzed 266 participants 267 participants 264 participants
-9.7  (0.7) -9.8  (0.7) -10.8  (0.7)
Week 16 Number Analyzed 253 participants 257 participants 251 participants
-10.0  (0.7) -10.9  (0.7) -11.9  (0.8)
Week 24 Number Analyzed 253 participants 257 participants 257 participants
-10.8  (0.8) -10.9  (0.8) -11.0  (0.9)
Week 36 Number Analyzed 245 participants 248 participants 243 participants
-13.5  (0.8) -12.7  (0.8) -12.9  (0.9)
Week 48 Number Analyzed 230 participants 239 participants 232 participants
-14.5  (0.8) -13.9  (0.8) -12.9  (0.9)
7.Secondary Outcome
Title Change From Baseline in Swollen Joint Count Over Time
Hide Description The swollen joint count is an assessment of the swelling of 66 joints using a 0 to 1 point scale (0 = none, 1 = present). The total swollen joint count is calculated by summing the number of joints with present swelling.
Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Mean (Standard Error)
Unit of Measure: swollen joints
Week 4 Number Analyzed 280 participants 279 participants 277 participants
-4.1  (0.4) -4.8  (0.3) -4.7  (0.4)
Week 8 Number Analyzed 271 participants 276 participants 269 participants
-5.4  (0.5) -6.2  (0.4) -6.5  (0.4)
Week 12 Number Analyzed 266 participants 267 participants 264 participants
-6.6  (0.5) -6.8  (0.4) -7.2  (0.4)
Week 16 Number Analyzed 253 participants 257 participants 251 participants
-7.0  (0.5) -7.3  (0.4) -7.8  (0.4)
Week 24 Number Analyzed 253 participants 257 participants 257 participants
-7.0  (0.5) -7.6  (0.5) -7.7  (0.5)
Week 36 Number Analyzed 245 participants 248 participants 243 participants
-9.2  (0.5) -9.0  (0.5) -8.4  (0.5)
Week 48 Number Analyzed 230 participants 239 participants 232 participants
-9.6  (0.5) -9.2  (0.5) -8.7  (0.5)
8.Secondary Outcome
Title Change From Baseline in Physician Global Assessment of Disease Activity Over Time
Hide Description A global assessment of the participant's arthritis assessed by the physician on a 100 mm visual analog scale (VAS) where 0 mm = No activity at all and 100 mm = Worst activity imaginable.
Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Mean (Standard Error)
Unit of Measure: mm
Week 4 Number Analyzed 278 participants 278 participants 277 participants
-16.8  (1.2) -23.1  (1.2) -22.8  (1.3)
Week 8 Number Analyzed 271 participants 277 participants 269 participants
-25.0  (1.4) -29.7  (1.4) -30.4  (1.4)
Week 12 Number Analyzed 266 participants 267 participants 264 participants
-26.8  (1.6) -32.7  (1.6) -33.9  (1.3)
Week 16 Number Analyzed 251 participants 257 participants 252 participants
-30.3  (1.7) -34.9  (1.5) -36.2  (1.4)
Week 24 Number Analyzed 250 participants 257 participants 257 participants
-29.6  (1.8) -35.7  (1.7) -35.8  (1.6)
Week 36 Number Analyzed 241 participants 246 participants 241 participants
-37.1  (1.7) -42.8  (1.5) -39.9  (1.5)
Week 48 Number Analyzed 229 participants 239 participants 232 participants
-41.4  (1.5) -43.8  (1.4) -41.5  (1.6)
9.Secondary Outcome
Title Change From Baseline in Patient Global Assessment of Disease Activity Over Time
Hide Description A global assessment of the participant's arthritis, assessed by the participant on a 100 mm VAS where 0 mm = No arthritis activity at all and 100 mm = Worst arthritis activity imaginable.
Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Mean (Standard Error)
Unit of Measure: mm
Week 4 Number Analyzed 280 participants 281 participants 277 participants
-11.0  (1.5) -21.9  (1.6) -21.0  (1.5)
Week 8 Number Analyzed 271 participants 277 participants 269 participants
-15.6  (1.6) -27.3  (1.6) -26.4  (1.6)
Week 12 Number Analyzed 266 participants 268 participants 264 participants
-18.6  (1.6) -29.9  (1.7) -28.0  (1.7)
Week 16 Number Analyzed 252 participants 257 participants 250 participants
-22.7  (1.7) -30.9  (1.7) -29.3  (1.7)
Week 24 Number Analyzed 252 participants 258 participants 257 participants
-23.0  (1.8) -32.3  (1.7) -29.6  (1.8)
Week 36 Number Analyzed 243 participants 248 participants 241 participants
-26.0  (1.8) -36.4  (1.8) -32.4  (1.8)
Week 48 Number Analyzed 228 participants 238 participants 232 participants
-28.9  (1.9) -38.8  (1.7) -33.3  (1.9)
10.Secondary Outcome
Title Change From Baseline in Patient Global Assessment of Joint Pain Over Time
Hide Description A global assessment of the severity of the participant's joint pain, assessed by the participant on a 100 mm VAS where 0 mm = No pain at all and 100 mm = Worst pain imaginable.
Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Mean (Standard Error)
Unit of Measure: mm
Week 4 Number Analyzed 280 participants 281 participants 277 participants
-8.9  (1.4) -18.4  (1.5) -18.5  (1.6)
Week 8 Number Analyzed 271 participants 277 participants 269 participants
-14.5  (1.5) -23.5  (1.5) -24.0  (1.5)
Week 12 Number Analyzed 266 participants 268 participants 264 participants
-16.0  (1.6) -24.1  (1.7) -24.9  (1.6)
Week 16 Number Analyzed 252 participants 257 participants 250 participants
-20.9  (1.7) -25.9  (1.7) -25.6  (1.7)
Week 24 Number Analyzed 252 participants 258 participants 257 participants
-20.6  (1.7) -26.4  (1.7) -26.9  (1.7)
Week 36 Number Analyzed 243 participants 248 participants 241 participants
-23.9  (1.7) -31.5  (1.7) -28.8  (1.8)
Week 48 Number Analyzed 228 participants 238 participants 232 participants
-27.2  (1.8) -32.5  (1.7) -31.1  (1.8)
11.Secondary Outcome
Title Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Over Time
Hide Description The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Mean (Standard Error)
Unit of Measure: units on a scale
Week 4 Number Analyzed 280 participants 281 participants 277 participants
-0.188  (0.024) -0.266  (0.024) -0.306  (0.029)
Week 8 Number Analyzed 271 participants 276 participants 269 participants
-0.277  (0.029) -0.365  (0.031) -0.403  (0.032)
Week 12 Number Analyzed 266 participants 268 participants 264 participants
-0.310  (0.030) -0.404  (0.029) -0.450  (0.033)
Week 16 Number Analyzed 252 participants 257 participants 250 participants
-0.378  (0.036) -0.454  (0.033) -0.483  (0.036)
Week 24 Number Analyzed 252 participants 258 participants 257 participants
-0.412  (0.036) -0.444  (0.035) -0.468  (0.038)
Week 36 Number Analyzed 243 participants 248 participants 241 participants
-0.452  (0.038) -0.496  (0.039) -0.548  (0.040)
Week 48 Number Analyzed 228 participants 238 participants 232 participants
-0.526  (0.041) -0.557  (0.038) -0.554  (0.041)
12.Secondary Outcome
Title Change From Baseline in C-reactive Protein Concentration Over Time
Hide Description C-reactive protein (CRP) is a specific measure of inflammatory activity.
Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Mean (Standard Error)
Unit of Measure: mg/L
Week 4 Number Analyzed 275 participants 265 participants 256 participants
-0.93  (0.93) -5.91  (1.01) -5.49  (0.74)
Week 8 Number Analyzed 270 participants 265 participants 257 participants
-2.31  (0.90) -7.51  (0.94) -5.19  (0.88)
Week 12 Number Analyzed 262 participants 255 participants 247 participants
-3.36  (0.84) -7.38  (0.99) -5.71  (0.82)
Week 16 Number Analyzed 248 participants 246 participants 241 participants
-2.81  (0.82) -7.40  (1.03) -5.59  (0.85)
Week 24 Number Analyzed 246 participants 249 participants 247 participants
-2.60  (0.91) -6.91  (1.15) -5.82  (0.70)
Week 36 Number Analyzed 236 participants 234 participants 230 participants
-4.16  (0.96) -7.36  (1.13) -5.82  (0.80)
Week 48 Number Analyzed 223 participants 226 participants 219 participants
-4.88  (1.03) -7.45  (1.10) -5.81  (0.95)
13.Secondary Outcome
Title Percentage of Participants With a American Minimal Disease Activity (MDA) Response Over Time
Hide Description

Minimal Disease Activity (MDA) is a measure of low disease activity specific for psoriatic arthritis (PsA) that incorporates measures of joint and entheseal inflammation, skin disease, patient reported outcomes and functional disability to assess disease activity. Participants were classified as achieving MDA if they fulfilled 5 of the following 7 outcome measures:

  • Tender joint count (0-68) ≤ 1
  • Swollen joint count (0-66) ≤ 1
  • Body surface area (BSA) involvement with psoriasis (0% to 100%) ≤ 3%
  • Patient global assessment of joint pain VAS (0-100) ≤ 15
  • Patient global assessment of disease activity VAS (0-100) ≤ 20
  • HAQ-DI (0-3) ≤ 0.5
  • Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index (18 sites assessed for enthesitis with an overall score of 0 - 16) ≤ 1
Time Frame Weeks 4, 8, 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Measure Type: Number
Unit of Measure: percentage of participants
Week 4 Number Analyzed 281 participants 280 participants 278 participants
5.7 11.1 12.6
Week 8 Number Analyzed 271 participants 276 participants 270 participants
3.0 9.4 7.4
Week 12 Number Analyzed 267 participants 268 participants 265 participants
11.6 29.9 29.1
Week 24 Number Analyzed 253 participants 258 participants 258 participants
25.7 39.5 39.1
Week 36 Number Analyzed 244 participants 248 participants 242 participants
30.3 43.5 46.7
Week 48 Number Analyzed 229 participants 238 participants 233 participants
35.8 51.3 53.2
14.Secondary Outcome
Title Change From Baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) Over Time
Hide Description

PASDAS is a measure of disease activity derived from the following variables:

  • Physician and patient global assessment of disease activity (assessed on a 0-100 VAS)
  • 68 tender joint count
  • 66 swollen joint count
  • Short Form-36 Questionnaire (SF-36) physical component summary (general health status on a scale from 0-100)
  • Tender dactylitis count (each digit assessed for tender dactylitis; total score 0-20)
  • Leeds enthesitis index (enthesitis assessed at 6 sites; total score of 0-6)
  • CRP level (mg/L)

The composite score is a weighted index where higher scores indicate more severe disease.

Time Frame Baseline and weeks 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Mean (Standard Error)
Unit of Measure: units on a scale
Week 12 Number Analyzed 261 participants 263 participants 261 participants
-1.63  (0.08) -2.32  (0.09) -2.37  (0.09)
Week 24 Number Analyzed 246 participants 250 participants 255 participants
-1.98  (0.10) -2.64  (0.10) -2.63  (0.11)
Week 36 Number Analyzed 234 participants 238 participants 232 participants
-2.46  (0.10) -3.10  (0.10) -2.95  (0.11)
Week 48 Number Analyzed 226 participants 232 participants 229 participants
-2.70  (0.10) -3.23  (0.09) -3.10  (0.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments Analysis of change from baseline in PASDAS at week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -0.62
Confidence Interval (2-Sided) 95%
-0.91 to -0.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments Analysis of change from baseline in PASDAS at week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is unadjusted and considered descriptive
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or >30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-0.92 to -0.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.15
Estimation Comments Methotrexate Monotherapy is the reference
15.Secondary Outcome
Title Change From Baseline in Clinical Disease Activity Index (CDAI) Over Time
Hide Description

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the following items:

  • 28 tender joint count,
  • 28 swollen joint count,
  • Patient's Global Assessment of Disease Activity measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest;
  • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest.

The CDAI score ranges from 0-76 where lower scores indicate less disease activity.

Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Mean (Standard Error)
Unit of Measure: units on a scale
Week 4 Number Analyzed 276 participants 277 participants 276 participants
-8.38  (0.62) -10.59  (0.61) -10.68  (0.60)
Week 8 Number Analyzed 270 participants 276 participants 268 participants
-11.56  (0.73) -14.13  (0.66) -14.56  (0.65)
Week 12 Number Analyzed 265 participants 266 participants 263 participants
-13.93  (0.74) -15.61  (0.75) -16.12  (0.71)
Week 16 Number Analyzed 250 participants 256 participants 248 participants
-15.20  (0.80) -16.49  (0.70) -17.37  (0.76)
Week 24 Number Analyzed 249 participants 257 participants 256 participants
-15.74  (0.85) -17.12  (0.78) -16.43  (0.85)
Week 36 Number Analyzed 240 participants 246 participants 239 participants
-18.90  (0.76) -19.79  (0.76) -18.86  (0.79)
Week 48 Number Analyzed 228 participants 238 participants 231 participants
-20.16  (0.80) -20.78  (0.75) -19.35  (0.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments Analysis of change from baseline in CDAI at week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.59
Comments P-value is unadjusted and considered descriptive
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-2.93 to 1.68
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.18
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments Analysis of change from baseline in CDAI at week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.26
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -1.32
Confidence Interval (2-Sided) 95%
-3.63 to 0.99
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.18
Estimation Comments Methotrexate Monotherapy is the reference
16.Secondary Outcome
Title Change From Baseline in Simplified Disease Activity Index (SDAI) Over Time
Hide Description

The Simplified Disease Activity Index (SDAI) is a composite index that is calculated as the sum of the following items:

  • 28 tender joint count,
  • 28 swollen joint count,
  • Patient's Global Assessment of Disease Activity measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest;
  • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest.
  • CRP

The SDAI score ranges from 0 to 86 with higher scores representing worse disease.

Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Mean (Standard Error)
Unit of Measure: units on a scale
Week 4 Number Analyzed 275 participants 273 participants 273 participants
-8.38  (0.62) -11.12  (0.62) -11.18  (0.61)
Week 8 Number Analyzed 270 participants 272 participants 267 participants
-11.77  (0.72) -14.92  (0.69) -15.14  (0.66)
Week 12 Number Analyzed 264 participants 264 participants 263 participants
-14.32  (0.75) -16.44  (0.77) -16.67  (0.73)
Week 16 Number Analyzed 248 participants 253 participants 246 participants
-15.55  (0.81) -17.25  (0.72) -17.79  (0.78)
Week 24 Number Analyzed 248 participants 253 participants 256 participants
-15.96  (0.86) -17.75  (0.81) -17.01  (0.87)
Week 36 Number Analyzed 239 participants 242 participants 235 participants
-19.27  (0.77) -20.50  (0.78) -19.46  (0.82)
Week 48 Number Analyzed 228 participants 234 participants 229 participants
-20.65  (0.81) -21.61  (0.77) -19.94  (0.87)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments Analysis of change from baseline in SDAI at week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.41
Comments P-value is unadjusted and considered descriptive
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -0.98
Confidence Interval (2-Sided) 95%
-3.35 to 1.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.20
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments Analysis of change from baseline in SDAI at week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -1.72
Confidence Interval (2-Sided) 95%
-4.09 to 0.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.21
Estimation Comments Methotrexate Monotherapy is the reference
17.Secondary Outcome
Title Change From Baseline in the Disease Activity Score 28 (DAS28) Over Time
Hide Description

The DAS28 measures the severity of disease at a specific time and is derived from the following variables:

  • 28 tender joint count
  • 28 swollen joint count
  • C-reactive protein (CRP)
  • Patient's global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.

DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.

Time Frame Baseline and weeks 4, 8, 12, 16, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing data at each time point
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 284 284 283
Mean (Standard Error)
Unit of Measure: units on a scale
Week 4 Number Analyzed 278 participants 275 participants 273 participants
-0.73  (0.05) -1.18  (0.06) -1.21  (0.06)
Week 8 Number Analyzed 270 participants 272 participants 267 participants
-1.05  (0.06) -1.64  (0.07) -1.61  (0.07)
Week 12 Number Analyzed 264 participants 265 participants 263 participants
-1.34  (0.06) -1.78  (0.08) -1.80  (0.08)
Week 16 Number Analyzed 250 participants 253 participants 246 participants
-1.47  (0.07) -1.90  (0.08) -1.92  (0.08)
Week 24 Number Analyzed 251 participants 253 participants 256 participants
-1.55  (0.08) -1.97  (0.08) -1.86  (0.08)
Week 36 Number Analyzed 242 participants 244 participants 236 participants
-1.88  (0.07) -2.25  (0.08) -2.20  (0.09)
Week 48 Number Analyzed 228 participants 234 participants 229 participants
-2.04  (0.07) -2.38  (0.08) -2.23  (0.09)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments Analysis of change from baseline in DAS28 at week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or >30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.52 to -0.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments Analysis of change from baseline in DAS28 at week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or >30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.62 to -0.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments Methotrexate Monotherapy is the reference
18.Secondary Outcome
Title Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24
Hide Description The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring in 8 functional areas: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with available data
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 252 258 257
Mean (Standard Error)
Unit of Measure: units on a scale
-0.412  (0.036) -0.444  (0.035) -0.468  (0.038)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.34
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or >30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.15 to 0.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.67
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.12 to 0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments Methotrexate Monotherapy is the reference
19.Secondary Outcome
Title Change From Baseline in Medical Outcomes Health Survey Short Form 36 Items Version 2 (SF-36 v2) at Week 24
Hide Description The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains. Two summary component scores are calculated: mental component summary score (MCS) and physical component summary score (PCS). The MCS consists of social functioning, vitality, mental health, and role-emotional scales and the PCS consists of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning.
Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with available data
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 253 256 257
Mean (Standard Error)
Unit of Measure: units on a scale
Physical Component Summary 5.952  (0.550) 7.808  (0.546) 8.011  (0.598)
Mental Component Summary 3.259  (0.589) 2.835  (0.624) 3.321  (0.572)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments Analysis of change from baseline in Physical Component Summary at week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or >30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 1.94
Confidence Interval (2-Sided) 95%
0.37 to 3.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.80
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments Analysis of change from baseline in Physical Component Summary at week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 1.71
Confidence Interval (2-Sided) 95%
0.13 to 3.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.80
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments Analysis of change from baseline in Mental Component Summary at week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.97
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-1.69 to 1.63
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.84
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments Analysis of change from baseline in Mental Component Summary at week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.56
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-2.16 to 1.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.85
Estimation Comments Methotrexate Monotherapy is the reference
20.Secondary Outcome
Title Change From Baseline in Modified Nail Psoriasis Severity Index (mNAPSI) at Week 24
Hide Description

The modified NAPSI scale is a grading system for nail psoriasis that incorporates the following 7 clinical features:

  • pitting (scores 0-3, depending on the number of pits)
  • nail plate crumbling (scores 0-3, depending on the % of nail involvement)
  • onycholysis and oil drop dyschromia (scores 0-3, depending on the % of nail involvement)
  • leukonychia (0 = absent, 1 = present)
  • red spots in lunula (0 = absent, 1 = present)
  • nail bed hyperkeratosis (0 = absent, 1 = present)
  • splinter hemorrhages (0 = absent, 1 = present)

In participants with fingernails involved with psoriasis, each fingernail was scored at baseline to determine the worst fingernail (ie, the fingernail with the highest mNAPSI score). This fingernail was followed for the remainder of the study.

mNAPSI scores range from 0-13 where higher scores represent worse nail disease.

Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with non-zero mNAPSI score at baseline and available data at week 24
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 121 115 123
Mean (Standard Error)
Unit of Measure: units on a scale
-1.1  (0.2) -1.5  (0.2) -1.7  (0.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or >30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -0.56
Confidence Interval (2-Sided) 95%
-1.03 to -0.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.24
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.88 to 0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.24
Estimation Comments Methotrexate Monotherapy is the reference
21.Secondary Outcome
Title Percentage of Participants With Clear mNAPSI at Week 24
Hide Description

The modified NAPSI scale is a grading system for nail psoriasis that incorporates the following 7 clinical features:

  • pitting (scores 0-3, depending on the number of pits)
  • nail plate crumbling (scores 0-3, depending on the % of nail involvement)
  • onycholysis and oil drop dyschromia (scores 0-3, depending on the % of nail involvement)
  • leukonychia (0 = absent, 1 = present)
  • red spots in lunula (0 = absent, 1 = present)
  • nail bed hyperkeratosis (0 = absent, 1 = present)
  • splinter hemorrhages (0 = absent, 1 = present)

In participants with fingernails involved with psoriasis, each fingernail was scored at baseline to determine the worst fingernail (ie, the fingernail with the highest mNAPSI score). This fingernail was followed for the remainder of the study.

mNAPSI scores range from 0-13 where higher scores represent worse nail disease. Clear mNAPSI is defined as a score = 0.

Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with non-zero mNAPSI score at baseline and available data at week 24
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 121 115 123
Measure Type: Number
Unit of Measure: percentage of participants
0.0 0.0 0.0
22.Secondary Outcome
Title Change From Baseline in Leeds Dactylitis Index (LDI) at Week 24
Hide Description The Leeds dactylitis index quantitatively measures dactylitis using the circumference of involved digits and control digits and tenderness of involved digits. Digits affected by dactylitis are defined as those with a 10% difference in the ratio of circumference of the affected digit to the contralateral digit. The control digit is either the contralateral digit (digit on opposite hand or foot), or if the contralateral digit is also affected, values from a standard reference table. Tenderness of affected digits is assessed on a scale from 0 [none] to 3 [worst]. The ratio of circumference between an affected digit and the control digit is multiplied by the tenderness score for the affected digit. The results from each involved digit are summed to provide the final LDI. A higher LDI indicates worse dactylitis.
Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with non-zero LDI score at baseline and available data at week 24
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 89 89 87
Mean (Standard Error)
Unit of Measure: units on a scale
-128.80  (26.76) -119.09  (20.66) -110.15  (22.70)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or >30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 13.92
Confidence Interval (2-Sided) 95%
-51.52 to 79.36
Parameter Dispersion
Type: Standard Error of the Mean
Value: 33.23
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.85
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 6.34
Confidence Interval (2-Sided) 95%
-58.75 to 71.42
Parameter Dispersion
Type: Standard Error of the Mean
Value: 33.05
Estimation Comments Methotrexate Monotherapy is the reference
23.Secondary Outcome
Title Percentage of Participants With Clear LDI at Week 24
Hide Description

The Leeds dactylitis index quantitatively measures dactylitis using the circumference of involved digits and control digits and tenderness of involved digits. Digits affected by dactylitis are defined as those with a 10% difference in the ratio of circumference of the affected digit to the contralateral digit. The control digit is either the contralateral digit (digit on opposite hand or foot), or if the contralateral digit is also affected, values from a standard reference table. Tenderness of affected digits is assessed on a scale from 0 [none] to 3 [worst]. The ratio of circumference between an affected digit and the control digit is multiplied by the tenderness score for the affected digit. The results from each involved digit are summed to provide the final LDI. A higher LDI indicates worse dactylitis.

Clear LDI is defined as a score = 0.

Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with non-zero LDI score at baseline and available data at week 24
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 89 89 87
Measure Type: Number
Unit of Measure: percentage of participants
65.2 76.4 79.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.057
Comments P-value is unadjusted and considered descriptive.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 12.9
Confidence Interval (2-Sided) 95%
-0.4 to 26.2
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments P-value is unadjusted and considered descriptive.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 10.9
Confidence Interval (2-Sided) 95%
-2.5 to 24.4
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
24.Secondary Outcome
Title Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index at Week 24
Hide Description The SPARCC enthesitis index assesses enthesitis at 18 sites for palpitation with a resultant total score of 0 to 16 (for scoring purposes, the inferior patella and tibial tuberosity are considered 1 site because of their anatomical proximity). Tenderness at each site is quantified on a dichotomous basis (0 = non-tender, 1 = tender). Entheses assessed are medial epicondyle (left and right), lateral epicondyle (left and right), supraspinatus insertion into greater tuberosity of humerus (left and right), greater trochanter (left and right), quadriceps insertion into superior border of patella (left and right), patellar ligament insertion into inferior pole of patella or tibial tubercle (left and right), Achilles tendon insertion into calcaneum (left and right), plantar fascia insertion into calcaneum (left and right). A higher count represents greater enthesitis burden.
Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with non-zero SPARCC enthesitis index score at baseline and available data at week 24
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 167 173 179
Mean (Standard Error)
Unit of Measure: units on a scale
-3.1  (0.3) -3.0  (0.3) -2.9  (0.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.70
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or >30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-0.66 to 0.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.42
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.93
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.79 to 0.86
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.42
Estimation Comments Methotrexate Monotherapy is the reference
25.Secondary Outcome
Title Percentage of Participants With Clear SPARCC Enthesitis Index Score at Week 24
Hide Description

The SPARCC enthesitis index assesses enthesitis at 18 sites for palpitation with a resultant total score of 0 to 16 (for scoring purposes, the inferior patella and tibial tuberosity are considered 1 site because of their anatomical proximity). Tenderness at each site is quantified on a dichotomous basis (0 = non-tender, 1 = tender). Entheses assessed are medial epicondyle (left and right), lateral epicondyle (left and right), supraspinatus insertion into greater tuberosity of humerus (left and right), greater trochanter (left and right), quadriceps insertion into superior border of patella (left and right), patellar ligament insertion into inferior pole of patella or tibial tubercle (left and right), Achilles tendon insertion into calcaneum (left and right), plantar fascia insertion into calcaneum (left and right). A higher count represents greater enthesitis burden.

Clear SPARCC enthesitis is defined as a score = 0.

Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with non-zero SPARCC enthesitis index score at baseline and available data at week 24
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 167 173 179
Measure Type: Number
Unit of Measure: percentage of participants
43.1 52.6 47.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.55
Comments P-value is unadjusted and considered descriptive.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
-7.3 to 13.7
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments P-value is unadjusted and considered descriptive.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 8.8
Confidence Interval (2-Sided) 95%
-1.9 to 19.4
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
26.Secondary Outcome
Title Percent Improvement From Baseline in the Percentage of Body Surface Area (BSA) Involved in Psoriasis at Week 24
Hide Description

The physician's assessment of the percentage of the participant's total body surface area involved with psoriasis.

Percent improvement from baseline = (Baseline Value - Post-baseline Value) / Baseline * 100

Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥ 3% body surface area (BSA) psoriasis involvement at baseline and available data.
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 179 166 163
Mean (Standard Error)
Unit of Measure: percent change
66.12  (2.76) 69.80  (2.73) 75.53  (3.71)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.031
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or >30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 9.36
Confidence Interval (2-Sided) 95%
0.85 to 17.87
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.33
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.49
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 3.02
Confidence Interval (2-Sided) 95%
-5.49 to 11.54
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.33
Estimation Comments Methotrexate Monotherapy is the reference
27.Secondary Outcome
Title Percent Improvement From Baseline in the Percentage of Body Surface Area (BSA) Involved in Psoriasis by Baseline BSA Involvement Subgroups
Hide Description

The physician's assessment of the percentage of the participant's total body surface area involved with psoriasis.

Percent improvement from baseline = (Baseline Value - Post-baseline Value) / Baseline * 100

Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with available BSA data
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 254 259 259
Mean (Standard Error)
Unit of Measure: percent change
< 3% BSA involvement at baseline Number Analyzed 75 participants 93 participants 96 participants
-24.49  (46.71) -92.18  (108.54) 17.66  (51.97)
≥ 3% to < 10% BSA involvement at baseline Number Analyzed 87 participants 75 participants 77 participants
66.61  (4.18) 64.42  (4.43) 68.76  (7.26)
≥ 10% BSA involvement at baseline Number Analyzed 92 participants 91 participants 86 participants
65.66  (3.66) 74.23  (3.32) 81.61  (2.55)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments Analysis of percent improvement from baseline in the percentage of BSA involved in psoriasis in the subgroup of participants with ≥ 10% BSA involvement at baseline.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 15.95
Confidence Interval (2-Sided) 95%
6.99 to 24.90
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.55
Estimation Comments Methotrexate Monotherapy is the reference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments Analysis of percent improvement from baseline in the percentage of BSA involved in psoriasis in the subgroup of participants with ≥ 10% BSA involvement at baseline.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments P-value is unadjusted and considered descriptive.
Method ANCOVA
Comments ANCOVA model adjusted for baseline BMI status (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD use.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 6.97
Confidence Interval (2-Sided) 95%
-1.89 to 15.83
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.50
Estimation Comments Methotrexate Monotherapy is the reference
28.Secondary Outcome
Title Static Physician Global Assessment (sPGA) at Week 24
Hide Description

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

  1. = almost clear (minimal plaque elevation, erythema or scaling)
  2. = mild (mild plaque elevation or scaling, light red coloration)
  3. = moderate (moderate plaque elevation, scaling, light red coloration)
  4. = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
  5. = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥ 3% body surface area (BSA) psoriasis involvement at baseline and available sPGA data.
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 178 166 161
Measure Type: Count of Participants
Unit of Measure: Participants
0 (clear)
38
  21.3%
36
  21.7%
63
  39.1%
1 (almost clear)
80
  44.9%
84
  50.6%
62
  38.5%
2 (mild)
34
  19.1%
28
  16.9%
25
  15.5%
3 (moderate)
22
  12.4%
12
   7.2%
10
   6.2%
4 (marked)
3
   1.7%
6
   3.6%
1
   0.6%
5 (severe)
1
   0.6%
0
   0.0%
0
   0.0%
29.Secondary Outcome
Title Static Physician Global Assessment (sPGA) at Week 24 by Baseline BSA Involvement Subgroups
Hide Description

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

  1. = almost clear (minimal plaque elevation, erythema or scaling)
  2. = mild (mild plaque elevation or scaling, light red coloration)
  3. = moderate (moderate plaque elevation, scaling, light red coloration)
  4. = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
  5. = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with available data
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 253 258 257
Measure Type: Count of Participants
Unit of Measure: Participants
< 3% BSA involvement at baseline Number Analyzed 75 participants 92 participants 96 participants
0 (clear)
26
  34.7%
29
  31.5%
52
  54.2%
1 (almost clear)
28
  37.3%
37
  40.2%
32
  33.3%
2 (mild)
15
  20.0%
19
  20.7%
9
   9.4%
3 (moderate)
4
   5.3%
6
   6.5%
3
   3.1%
4 (marked)
2
   2.7%
1
   1.1%
0
   0.0%
5 (severe)
0
   0.0%
0
   0.0%
0
   0.0%
≥ 3% to < 10% BSA involvement at baseline Number Analyzed 87 participants 75 participants 76 participants
0 (clear)
23
  26.4%
16
  21.3%
35
  46.1%
1 (almost clear)
41
  47.1%
32
  42.7%
23
  30.3%
2 (mild)
13
  14.9%
18
  24.0%
12
  15.8%
3 (moderate)
10
  11.5%
7
   9.3%
5
   6.6%
4 (marked)
0
   0.0%
2
   2.7%
1
   1.3%
5 (severe)
0
   0.0%
0
   0.0%
0
   0.0%
≥ 10% BSA involvement at baseline Number Analyzed 91 participants 91 participants 85 participants
0 (clear)
15
  16.5%
20
  22.0%
28
  32.9%
1 (almost clear)
39
  42.9%
52
  57.1%
39
  45.9%
2 (mild)
21
  23.1%
10
  11.0%
13
  15.3%
3 (moderate)
12
  13.2%
5
   5.5%
5
   5.9%
4 (marked)
3
   3.3%
4
   4.4%
0
   0.0%
5 (severe)
1
   1.1%
0
   0.0%
0
   0.0%
30.Secondary Outcome
Title Mean Static Physician Global Assessment (sPGA) Score at Week 24
Hide Description

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

  1. = almost clear (minimal plaque elevation, erythema or scaling)
  2. = mild (mild plaque elevation or scaling, light red coloration)
  3. = moderate (moderate plaque elevation, scaling, light red coloration)
  4. = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
  5. = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥ 3% body surface area (BSA) psoriasis involvement at baseline and available sPGA data.
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 178 166 161
Mean (Standard Error)
Unit of Measure: units on a scale
1.3  (0.1) 1.2  (0.1) 0.9  (0.1)
31.Secondary Outcome
Title Mean Static Physician Global Assessment (sPGA) Score at Week 24 by Baseline BSA Involvement Subgroups
Hide Description

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

  1. = almost clear (minimal plaque elevation, erythema or scaling)
  2. = mild (mild plaque elevation or scaling, light red coloration)
  3. = moderate (moderate plaque elevation, scaling, light red coloration)
  4. = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
  5. = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with available data
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 253 258 257
Mean (Standard Error)
Unit of Measure: units on a scale
< 3% BSA involvement at baseline Number Analyzed 75 participants 92 participants 96 participants
1.0  (0.1) 1.1  (0.1) 0.6  (0.1)
≥ 3% to < 10% BSA involvement at baseline Number Analyzed 87 participants 75 participants 76 participants
1.1  (0.1) 1.3  (0.1) 0.9  (0.1)
≥ 10% BSA involvement at baseline Number Analyzed 91 participants 91 participants 85 participants
1.5  (0.1) 1.1  (0.1) 0.9  (0.1)
32.Secondary Outcome
Title Percentage of Participants With an sPGA Score of 0 (Clear) or 1 (Almost Clear) at Week 24
Hide Description

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

  1. = almost clear (minimal plaque elevation, erythema or scaling)
  2. = mild (mild plaque elevation or scaling, light red coloration)
  3. = moderate (moderate plaque elevation, scaling, light red coloration)
  4. = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
  5. = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥ 3% body surface area (BSA) psoriasis involvement at baseline and available sPGA data.
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 178 166 161
Measure Type: Number
Unit of Measure: percentage of participants
66.3 72.3 77.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments P-value is unadjusted and considered descriptive.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 11.4
Confidence Interval (2-Sided) 95%
2.0 to 20.8
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments P-value is unadjusted and considered descriptive.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 4.2
Confidence Interval (2-Sided) 95%
-5.6 to 14.0
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
33.Secondary Outcome
Title Percentage of Participants With an sPGA Score of 0 (Clear) or 1 (Almost Clear) at Week 24 by Baseline BSA Involvement Subgroups
Hide Description

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

  1. = almost clear (minimal plaque elevation, erythema or scaling)
  2. = mild (mild plaque elevation or scaling, light red coloration)
  3. = moderate (moderate plaque elevation, scaling, light red coloration)
  4. = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
  5. = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with available data
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 253 258 257
Measure Type: Number
Unit of Measure: percentage of participants
< 3% BSA involvement at baseline Number Analyzed 75 participants 92 participants 96 participants
72.0 71.7 87.5
≥ 3% to < 10% BSA involvement at baseline Number Analyzed 87 participants 75 participants 76 participants
73.6 64.0 76.3
≥ 10% BSA involvement at baseline Number Analyzed 91 participants 91 participants 85 participants
59.3 79.1 78.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept + Methotrexate
Comments Analysis of percentage of participants with an sPGA of 0 or 1 at Week 24 in participants with baseline BSA involvement with psoriasis ≥ 10%.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments P-value is unadjusted and considered descriptive.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 20.1
Confidence Interval (2-Sided) 95%
6.8 to 33.3
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methotrexate Monotherapy, Etanercept Monotherapy
Comments Analysis of percentage of participants with an sPGA of 0 or 1 at Week 24 in participants with baseline BSA involvement with psoriasis ≥ 10%.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments P-value is unadjusted and considered descriptive.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with baseline body mass index (≤ 30 kg/m² or > 30 kg/m²) and prior non-biologic DMARD treatment as stratification factors
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 17.1
Confidence Interval (2-Sided) 95%
4.0 to 30.2
Estimation Comments The risk difference was estimated using the Mantel-Haenszel estimate of common risk difference using the stratification factors described above.
34.Secondary Outcome
Title Percentage of Participants With at Least a 1 Grade Improvement in sPGA From Baseline at Week 24
Hide Description

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

  1. = almost clear (minimal plaque elevation, erythema or scaling)
  2. = mild (mild plaque elevation or scaling, light red coloration)
  3. = moderate (moderate plaque elevation, scaling, light red coloration)
  4. = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
  5. = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).
Time Frame Baseline and week 24
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Hide Analysis Population Description
Randomized participants with ≥ 3% body surface area (BSA) psoriasis involvement at baseline and available sPGA data.
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 177 166 161
Measure Type: Number
Unit of Measure: percentage of participants
29.9 28.9 18.0
35.Secondary Outcome
Title Percentage of Participants With at Least a 1 Grade Improvement in sPGA From Baseline at Week 24 by Baseline BSA Involvement Subgroups
Hide Description

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

  1. = almost clear (minimal plaque elevation, erythema or scaling)
  2. = mild (mild plaque elevation or scaling, light red coloration)
  3. = moderate (moderate plaque elevation, scaling, light red coloration)
  4. = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
  5. = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).
Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with available data
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 250 258 257
Measure Type: Number
Unit of Measure: percentage of participants
< 3% BSA involvement at baseline Number Analyzed 73 participants 92 participants 96 participants
37.0 44.6 43.8
≥ 3% to < 10% BSA involvement at baseline Number Analyzed 86 participants 75 participants 76 participants
27.9 38.7 21.1
≥ 10% BSA involvement at baseline Number Analyzed 91 participants 91 participants 85 participants
31.9 20.9 15.3
36.Secondary Outcome
Title Percentage of Participants With at Least a 2 Grade Improvement in sPGA From Baseline at Week 24
Hide Description

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

  1. = almost clear (minimal plaque elevation, erythema or scaling)
  2. = mild (mild plaque elevation or scaling, light red coloration)
  3. = moderate (moderate plaque elevation, scaling, light red coloration)
  4. = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
  5. = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).
Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥ 3% body surface area (BSA) psoriasis involvement at baseline and available sPGA data.
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 177 166 161
Measure Type: Number
Unit of Measure: percentage of participants
30.5 28.9 35.4
37.Secondary Outcome
Title Percentage of Participants With at Least a 2 Grade Improvement in sPGA From Baseline at Week 24 by Baseline BSA Involvement Subgroups
Hide Description

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

  1. = almost clear (minimal plaque elevation, erythema or scaling)
  2. = mild (mild plaque elevation or scaling, light red coloration)
  3. = moderate (moderate plaque elevation, scaling, light red coloration)
  4. = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
  5. = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).
Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with available data
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description:
Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks.
Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks.
Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
Overall Number of Participants Analyzed 250 258 257
Measure Type: Number
Unit of Measure: percentage of participants
< 3% BSA involvement at baseline Number Analyzed 73 participants 92 participants 96 participants
15.1 20.7 30.2
≥ 3% to < 10% BSA involvement at baseline Number Analyzed 86 participants 75 participants 76 participants
34.9 25.3 32.9
≥ 10% BSA involvement at baseline Number Analyzed 91 participants 91 participants 85 participants
26.4 31.9 37.6
Time Frame 48-week treatment period plus 30-day safety follow-up
Adverse Event Reporting Description

Two participants randomized to the Etanercept Monotherapy arm also received methotrexate in error, so are counted in the Etanercept + Methotrexate group for safety.

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

 
Arm/Group Title Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Hide Arm/Group Description Participants received oral methotrexate 20 mg weekly plus placebo to etanercept subcutaneous injection once a week for 48 weeks. Participants received etanercept 50 mg weekly by subcutaneous injection plus oral placebo to methotrexate for 48 weeks. Participants received etanercept 50 mg a week by subcutaneous injection and oral methotrexate 20 mg a week for 48 weeks.
All-Cause Mortality
Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/282 (0.00%)   0/282 (0.00%)   0/284 (0.00%) 
Hide Serious Adverse Events
Methotrexate Monotherapy Etanercept Monotherapy Etanercept + Methotrexate
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   16/282 (5.67%)   19/282 (6.74%)   17/284 (5.99%) 
Cardiac disorders       
Acute myocardial infarction  1  2/282 (0.71%)  0/282 (0.00%)  0/284 (0.00%) 
Angina unstable  1  0/282 (0.00%)  1/282 (0.35%)  0/284 (0.00%) 
Cardiac failure congestive  1  0/282 (0.00%)  1/282 (0.35%)  0/284 (0.00%) 
Cardiomyopathy  1  0/282 (0.00%)  1/282 (0.35%)  0/284 (0.00%) 
Coronary artery disease  1  0/282 (0.00%)  1/282 (0.35%)  0/284 (0.00%) 
Supraventricular tachyarrhythmia  1  0/282 (0.00%)  0/282 (0.00%)  1/284 (0.35%) 
Gastrointestinal disorders       
Gastric ulcer  1  1/282 (0.35%)  0/282 (0.00%)  0/284 (0.00%) 
Gastritis  1  0/282 (0.00%)  0/282 (0.00%)  1/284 (0.35%) 
Pancreatitis acute  1  1/282 (0.35%)  0/282 (0.00%)  0/284 (0.00%) 
General disorders       
Non-cardiac chest pain  1  0/282 (0.00%)  0/282 (0.00%)  2/284 (0.70%) 
Hepatobiliary disorders       
Cholecystitis acute  1  0/282 (0.00%)  0/282 (0.00%)  1/284 (0.35%) 
Drug-induced liver injury  1  0/282 (0.00%)  1/282 (0.35%)  0/284 (0.00%) 
Hyperbilirubinaemia  1  1/282 (0.35%)  0/282 (0.00%)  0/284 (0.00%) 
Liver injury  1  1/282 (0.35%)  0/282 (0.00%)  0/284 (0.00%) 
Infections and infestations       
Acute pulmonary histoplasmosis  1  1/282 (0.35%)  0/282 (0.00%)  0/284 (0.00%) 
Appendicitis  1  0/282 (0.00%)  0/282 (0.00%)  2/284 (0.70%) 
Bronchitis  1  0/282 (0.00%)  2/282 (0.71%)  1/284 (0.35%) 
Cellulitis  1  0/282 (0.00%)  2/282 (0.71%)  0/284 (0.00%) 
Chronic sinusitis  1  0/282 (0.00%)  1/282 (0.35%)  0/284 (0.00%) 
Escherichia urinary tract infection  1  0/282 (0.00%)  0/282 (0.00%)  1/284 (0.35%) 
Influenza  1  0/282 (0.00%)  0/282 (0.00%)  1/284 (0.35%) 
Necrotising fasciitis streptococcal  1  0/282 (0.00%)  1/282 (0.35%)  0/284 (0.00%) 
Peritonsillar abscess  1  0/282 (0.00%)  1/282 (0.35%)  0/284 (0.00%) 
Pneumonia bacterial  1  0/282 (0.00%)  0/282 (0.00%)  1/284 (0.35%) 
Pneumonia necrotising  1  0/282 (0.00%)  0/282 (0.00%)  1/284 (0.35%) 
Post procedural sepsis  1  0/282 (0.00%)  0/282 (0.00%)  1/284 (0.35%) 
Sinusitis  1  0/282 (0.00%)  1/282 (0.35%)  0/284 (0.00%) 
Urinary tract infection  1  2/282 (0.71%)  0/282 (0.00%)  0/284 (0.00%) 
Injury, poisoning and procedural complications       
Anaemia postoperative  1  0/282 (0.00%)  0/282 (0.00%)  1/284 (0.35%) 
Foreign body  1  0/282 (0.00%)  1/282 (0.35%)  0/284 (0.00%) 
Investigations