A Phase 4 interventional study of etanercept in Active Rheumatoid Arthritis, Arthritis, Rheumatoid and Rheumatoid Arthritis, sponsored by Pfizer. Completed at 58 sites in 13 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-07-17.
Sponsored by Pfizer · Phase 4, Interventional, and Treatment
Study to evaluate whether there is sustained remission and productivity in subjects with early rheumatoid arthritis started on etanercept plus methotrexate treatment.
3,554 studies on the registry are indexed under Arthritis; 318 are open to participants now.
This study's enrollment of 306 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.
Browse Arthritis studies →Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
etanercept + methotrexate; etanercept + methotrexate
Drug: etanercept
Also known as: Enbrel
Number of Participants That Met Sustained Remission at Week 76 and Week 91 Based on DAS28 Score
Sustained remission was defined as a DAS28 \<2.6 at the Week 76 and Week 91 visits without requiring a corticosteroid boost between the Week 52 and Week 64 visits, where the requirement for a corticosteroid boost was defined as a value of DAS28 \>3.2 at either the Week 56 or Week 64 visit. DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity. The participants who met sustained remission in both Week 76 and 91 are presented here.
Time frame: 76 and 91 weeks
Number of Participants Achieving Complete Response (Using Disease Activity Score Based on 28-joint Count, Modified Total Sharp Score, Health Assessment Questionnaire)
The composite measure of complete response over the last 3 months of Phase 1 was defined as: 1. DAS28 \<2.6 at the week 39 and 52 visits and, 2. No radiographic progression during Phase 1, defined as mean change in modified total Sharp score (mTSS) ≤0.5 and, 3. Health Assessment Questionnaire (HAQ) ≤ 0.5 at the week 39 and week 52 visits
Time frame: End of Phase 1
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52 and Final on Therapy
mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at baseline. An increase in mTSS from baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: 52 week and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire: Percent Overall Work Impairment Due to Problem
WPAI:6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived:percentage of absenteeism, percentage of presenteeism (reduced productivity while at work),overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw scores (0-10) are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
Time frame: 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire: Percent Impairment While Working Due to Problem
WPAI:6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived:percentage of absenteeism, percentage of presenteeism (reduced productivity while at work),overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw scores (0-10) are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
Time frame: 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire: Percent Work Time Missed Due to Problem
WPAI:6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived:percentage of absenteeism, percentage of presenteeism (reduced productivity while at work),overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw scores (0-10) are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
Time frame: 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire: Percent Activity Impairment Due to Problem
WPAI:6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived:percentage of absenteeism, percentage of presenteeism (reduced productivity while at work),overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw scores (0-10) are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
Time frame: 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Number of Participants Achieving American College of Rhematology 20% (ACR 20) Response
ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Time frame: 2, 4, 8, 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Number of Participants Achieving American College of Rhematology 50% (ACR 50) Response
ACR50 response: greater than or equal to (≥) 50 percent (%) improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Time frame: 2, 4, 8, 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Number of Participants Achieving American College of Rhematology 70% (ACR 70) Response
ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Time frame: 2, 4, 8, 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Number of Participants Achieving American College of Rhematology 90% (ACR 90) Response
ACR90 response: greater than or equal to (≥) 90 percent (%) improvement in tender or swollen joint counts and 90% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Time frame: 2, 4, 8, 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Change From Baseline in Physician's Global Assessment of Disease Activity
Physician Global Assessment of Disease Activity was measured on a 0 to 100 Visual Analog Scale (VAS), with 0 = no disease activity and 100 = extreme disease activity.
Time frame: 2, 4, 8, 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Change From Baseline in Participant's Global Assessment of Disease Activity
Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = no disease activity and 100 = extreme disease activity
Time frame: 2, 4, 8, 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Change From Baseline in DAS44 Score at All Visits
DAS44 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 44 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS44 \<1.6 = clinical remission, DAS44 ≤2.4 = low disease activity.
Time frame: 2, 4, 8, 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Number of Participants With Disease Activity Score Based on 44-joints Count (DAS44)-Remission
DAS44 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 44 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS44 \<1.6 = clinical remission, DAS44 ≤2.4 = low disease activity.
Time frame: 2, 4, 8, 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Number of Participants With Disease Activity Score Based on 44-joints Count (DAS44) - Low Disease Activity
DAS44 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 44 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS44 \<1.6 = clinical remission, DAS44 ≤2.4 = low disease activity.
Time frame: 2, 4, 8, 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Proportion of Subjects Achieving a Patient Acceptable Symptom State (PASS) at Each Visit
The PASS is defined as a symptom state that the participants consider acceptable.
Time frame: 2, 4, 8, 13, 26, 39, 52 weeks and Final on Therapy (includes all visits for a participant up to Week 52 or the visit they discontinued at)
Number of Participants With an American College of Rheumatology 20% (ACR20) Response
ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).
Time frame: 52, 56, 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant up to Week 91 or the visit they discontinued at)
Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response
ACR50 response: greater than or equal to (≥) 50 percent (%) improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Time frame: 52, 56, 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant up to Week 91 or the visit they discontinued at)
Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response
ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Time frame: 52, 56, 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant up to Week 91 or the visit they discontinued at)
Number of Participants Achieving American College of Rheumatology 90% (ACR90) Response
ACR90 response: greater than or equal to (≥) 90 percent (%) improvement in tender or swollen joint counts and 90% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Time frame: 52, 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant up to Week 91 or the visit they discontinued at)
Number of Participants With Disease Activity Score Based on 44-joints Count (DAS44) Remission
DAS44 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 44 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS44 \<1.6 = clinical remission, DAS44 ≤2.4 = low disease activity.
Time frame: 52, 56, 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant up to Week 91 or the visit they discontinued at)
Number of Participants With Disease Activity Score Based on 44-joints Count (DAS44) - Low Disease Activity
DAS44 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 44 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS44 \<1.6 = clinical remission, DAS44 ≤2.4 = low disease activity.
Time frame: 52, 56, 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant up to Week 91 or the visit they discontinued at)
Number of Participants Achieving Complete Response (Using Disease Activity Score Based on a 28-joint Count, Modified Total Sharp Score, Health Assessment Questionnaire)
The composite measure of complete response over the last 3 months of Phase 2 was defined as: 1. DAS28 \<2.6 at the Week 76 and Week 91 visits and 2. No radiographic progression during Phase 2, defined as mean change from Week 52 in mTSS of ≤0.5. 3. Participant must achieve HAQ score ≤0.5 at Week 76 and 91 visits. HAQ is self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation.A subject had to satisfy all 3 criteria at thevisits to be defined as a responder
Time frame: 52 and 91 weeks
Physician's Global Assessment of Disease Activity
Physician Global Assessment of Disease Activity was measured on a 0 to 100 Visual Analog Scale (VAS), with 0 = no disease activity and 100 = extreme disease activity.
Time frame: 52, 56, 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant up to Week 91 or the visit they discontinued at)
Participant's Global Assessment of Disease Activity
Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = no disease activity and 100 = extreme disease activity
Time frame: 52, 56, 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant up to Week 91 or the visit they discontinued at)
Participant's Global Assessment of Pain (Visual Analogue Scale) (VAS)
100-mm line (Visual Analog Scale) marked by the participant to measure their degree of pain over past 2-3 weeks. Range: 0 = no pain to 100 = pain as bad as it could be.
Time frame: 52, 56, 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant up to Week 91 or the visit they discontinued at)
Number of Participants Achieving Patient Acceptable Symptom State (PASS)
The PASS is defined as a symptom state that the subjects consider acceptable.
Time frame: 52, 56, 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant up to Week 91 or the visit they discontinued at)
Modified Total Sharp Score (mTSS) at Week 52
mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: 52 weeks
Change From Baseline mTSS at Week 91 and Final on Therapy
mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: 91 weeks and Final on Therapy (includes all visits for a participant up to Week 91 or the visit they discontinued at)
Work Productivity and Activity Impairment (WPAI) Questionnaire: Percent Work Time Missed in the Past 7 Days Due to Problem
WPAI: 6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw (0-10) scores are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
Time frame: 52 weeks
Change From Baseline in WPAI Questionnaire: Percent Work Time Missed in the Past 7 Days Due to Problem
WPAI is a 6 question participant rated questionnaire determined the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores = greater impairment and less productivity. The raw (0-10) scores were converted to percent (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
Time frame: 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant upto Week 91 or the visit they discontinued at)
WPAI Questionnaire: Percent Impairment While Working in the Past 7 Days Due to Problem
WPAI: 6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw (0-10) scores are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
Time frame: 52 Weeks
Change From Baseline in WPAI Questionnaire: Percent Impairment While Working in the Past 7 Days Due to Problem
WPAI: 6 question participant rated questionnaire determined the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores = greater impairment and less productivity. The raw (0-10) scores were converted to percent (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
Time frame: 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant upto Week 91 or the visit they discontinued at)
WPAI Questionnaire: Percent Overall Work Impairment in the Past 7 Days Due to Problem
WPAI: 6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw (0-10) scores are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
Time frame: 52 weeks
Change From Baseline in WPAI Questionnaire: Percent Overall Work Impairment in the Past 7 Days Due to Problem
WPAI: 6 question participant rated questionnaire determined the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores = greater impairment and less productivity. The raw (0-10) scores were converted to percent (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
Time frame: 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant upto Week 91 or the visit they discontinued at)
WPAI Questionnaire: Percent Activity Impairment in the Past 7 Days Due to Problem
WPAI: 6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw (0-10) scores are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
Time frame: 52 weeks
Change From Baseline in WPAI Questionnaire: Percent Activity Impairment in the Past 7 Days Due to Problem
WPAI: 6 question participant rated questionnaire determined the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores = greater impairment and less productivity. The raw (0-10) scores were converted to percent (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
Time frame: 64, 76, 91 weeks and Final on Therapy (includes all visits for a participant upto Week 91 or the visit they discontinued at)
This report presents the results of open-label 52-week treatment period (Phase 1), 39 week, double blind randomized (Phase 2) and 26 week observational period (Phase 3) part of a 121 week Phase 4 study program. Responders in Phase 1 were randomized to 3 arms (1:1:1 ratio) in Phase 2. Responders in Phase 2, continued to Phase 3 observational period
| Milestone | ETN 50 QW + MTX (Phase 1) | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) | E25+MTX (Phase 3) | MTX (Phase 3) | Placebo (PBO) (Phase 3) |
|---|---|---|---|---|---|---|---|
| Started | 306 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 194 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 112 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Non-responder | 54 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Subject request | 17 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Adverse event | 20 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Protocol violation | 10 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Sponsor | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Unsatisfactory response per investigator | 7 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | ETN 50 QW + MTX (Phase 1) | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) | E25+MTX (Phase 3) | MTX (Phase 3) | Placebo (PBO) (Phase 3) |
|---|---|---|---|---|---|---|---|
| Started | 0 | 63 | 65 | 65 | 0 | 0 | 0 |
| Completed | 0 | 53 | 46 | 32 | 0 | 0 | 0 |
| Not completed | 0 | 10 | 19 | 33 | 0 | 0 | 0 |
| Withdrew: Non-responder | 0 | 5 | 7 | 12 | 0 | 0 | 0 |
| Withdrew: Subject request | 0 | 0 | 1 | 2 | 0 | 0 | 0 |
| Withdrew: Adverse event | 0 | 3 | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Protocol violation | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Unsatisfactory response per investigator | 0 | 0 | 11 | 17 | 0 | 0 | 0 |
| Milestone | ETN 50 QW + MTX (Phase 1) | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) | E25+MTX (Phase 3) | MTX (Phase 3) | Placebo (PBO) (Phase 3) |
|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 53 | 46 | 32 |
| Completed | 0 | 0 | 0 | 0 | 31 | 28 | 24 |
| Not completed | 0 | 0 | 0 | 0 | 22 | 18 | 8 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 5 | 4 | 1 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Withdrew: Non-responder | 0 | 0 | 0 | 0 | 0 | 1 | 3 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 1 | 2 | 0 |
| Withdrew: Unsatisfactory response per investigator | 0 | 0 | 0 | 0 | 14 | 11 | 4 |
Sustained remission was defined as a DAS28 \<2.6 at the Week 76 and Week 91 visits without requiring a corticosteroid boost between the Week 52 and Week 64 visits, where the requirement for a corticosteroid boost was defined as a value of DAS28 \>3.2 at either the Week 56 or Week 64 visit. DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity. The participants who met sustained remission in both Week 76 and 91 are presented here.
| Participants | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Number of Participants That Met Sustained Remission at Week 76 and Week 91 Based on DAS28 Score | 40 | 26 | 15 |
The composite measure of complete response over the last 3 months of Phase 1 was defined as: 1. DAS28 \<2.6 at the week 39 and 52 visits and, 2. No radiographic progression during Phase 1, defined as mean change in modified total Sharp score (mTSS) ≤0.5 and, 3. Health Assessment Questionnaire (HAQ) ≤ 0.5 at the week 39 and week 52 visits
| Participants | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Number of Participants Achieving Complete Response (Using Disease Activity Score Based on 28-joint Count, Modified Total Sharp Score, Health Assessment Questionnaire) | 89 |
mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at baseline. An increase in mTSS from baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
| Units on a scale | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 52 (N = 200) | 0.3 ± 3.0 |
| Final on Therapy (N = 269) | 0.4 ± 2.8 |
WPAI:6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived:percentage of absenteeism, percentage of presenteeism (reduced productivity while at work),overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw scores (0-10) are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
| units on a scale | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 13 (N = 100) | -27.6 ± 27.4 |
| Week 26 (N = 94) | -32.2 ± 28.0 |
| Week 39 (N = 97) | -35.9 ± 27.0 |
| Week 52 (N = 81) | -37.3 ± 30.7 |
| Final on Therapy (N = 124) | -35.5 ± 31.3 |
WPAI:6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived:percentage of absenteeism, percentage of presenteeism (reduced productivity while at work),overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw scores (0-10) are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
| units on a scale | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 13 (N = 140) | -27.1 ± 27.8 |
| Week 26 (N = 138) | -31.5 ± 28.0 |
| Week 39 (N = 129) | -35.3 ± 27.3 |
| Week 52 (N = 116) | -36.6 ± 31.5 |
| Final on Therapy (N = 169) | -33.7 ± 30.3 |
WPAI:6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived:percentage of absenteeism, percentage of presenteeism (reduced productivity while at work),overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw scores (0-10) are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
| units on a scale | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 13 (N = 116) | -8.9 ± 34.5 |
| Week 26 (N = 110) | -8.8 ± 32.5 |
| Week 39 (N = 110) | -9.0 ± 30.7 |
| Week 52 (N = 93) | -12.9 ± 32.4 |
| Final on Therapy (N = 138) | -10.7 ± 35.3 |
WPAI:6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived:percentage of absenteeism, percentage of presenteeism (reduced productivity while at work),overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw scores (0-10) are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
| units on a scale | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 13 (N = 244) | -30.3 ± 26.0 |
| Week 26 (N = 241) | -34.7 ± 27.5 |
| Week 39 (N = 224) | -39.9 ± 27.0 |
| Week 52 (N = 194) | -41.3 ± 28.6 |
| Final on Therapy (N = 270) | -36.4 ± 29.4 |
ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
| Participants | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 2 (N = 297) | 139 |
| Week 4 (N = 295) | 195 |
| Week 8 (N = 290) | 225 |
| Week 13 (N = 280) | 232 |
| Week 26 (N = 272) | 232 |
| Week 39 (N = 256) | 235 |
| Week 52 (N = 221) | 212 |
| Final on Therapy (N = 301) | 258 |
ACR50 response: greater than or equal to (≥) 50 percent (%) improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
| Participants | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 2 (N = 297) | 52 |
| Week 4 (N = 295) | 114 |
| Week 8 (N = 290) | 144 |
| Week 13 (N = 280) | 169 |
| Week 26 (N = 272) | 190 |
| Week 39 (N = 256) | 218 |
| Week 52 (N = 221) | 202 |
| Final on Therapy (N = 301) | 229 |
ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
| Participants | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 2 (N = 297) | 17 |
| Week 4 (N = 295) | 49 |
| Week 8 (N = 290) | 80 |
| Week 13 (N = 280) | 115 |
| Week 26 (N = 272) | 146 |
| Week 39 (N = 256) | 178 |
| Week 52 (N = 221) | 176 |
| Final on Therapy (N = 301) | 198 |
ACR90 response: greater than or equal to (≥) 90 percent (%) improvement in tender or swollen joint counts and 90% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
| Participants | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 2 (N = 297) | 2 |
| Week 4 (N = 295) | 11 |
| Week 8 (N = 290) | 22 |
| Week 13 (N = 280) | 34 |
| Week 26 (N = 272) | 70 |
| Week 39 (N = 256) | 85 |
| Week 52 (N = 221) | 97 |
| Final on Therapy (N = 301) | 105 |
Physician Global Assessment of Disease Activity was measured on a 0 to 100 Visual Analog Scale (VAS), with 0 = no disease activity and 100 = extreme disease activity.
| Units on a scale | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 2 (N = 300) | -21.1 ± 18.2 |
| Week 4 (N = 299) | -29.9 ± 19.7 |
| Week 8 (N = 294) | -34.8 ± 19.9 |
| Week 13 (N = 284) | -38.7 ± 20.0 |
| Week 26 (N = 277) | -42.4 ± 18.9 |
| Week 39 (N = 260) | -46.5 ± 18.5 |
| Week 52 (N = 223) | -49.2 ± 17.2 |
| Final on Therapy (N = 305) | -45.0 ± 19.8 |
Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = no disease activity and 100 = extreme disease activity
| units on a scale | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 2 (N = 301) | -23.4 ± 24.4 |
| Week 4 (N = 299) | -27.4 ± 26.2 |
| Week 8 (N = 294) | -31.8 ± 26.0 |
| Week 13 (N = 285) | -34.6 ± 26.8 |
| Week 26 (N = 277) | -40.1 ± 28.1 |
| Week 39 (N = 260) | -44.8 ± 26.6 |
| Week 52 (N = 233) | -48.6 ± 26.2 |
| Final on Therapy (N = 305) | -42.8 ± 28.4 |
DAS44 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 44 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS44 \<1.6 = clinical remission, DAS44 ≤2.4 = low disease activity.
| units on a scale | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 2 (N = 297) | -1.3 ± 0.9 |
| Week 4 (N = 293) | -1.9 ± 1.1 |
| Week 8 (N = 293) | -2.3 ± 1.1 |
| Week 13 (N = 282) | -2.5 ± 1.2 |
| Week 26 (N = 276) | -2.9 ± 1.2 |
| Week 39 (N = 259) | -3.2 ± 1.2 |
| Week 52 (N = 221) | -3.4 ± 1.2 |
| Final on Therapy (N = 305) | -3.0 ± 1.3 |
DAS44 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 44 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS44 \<1.6 = clinical remission, DAS44 ≤2.4 = low disease activity.
| Participants | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 2 (N = 297) | 13 |
| Week 4 (N = 293) | 48 |
| Week 8 (N = 293) | 81 |
| Week 13 (N = 282) | 95 |
| Week 26 (N = 276) | 142 |
| Week 39 (N = 259) | 174 |
| Week 52 (N = 221) | 193 |
| Final on Therapy (N = 305) | 211 |
DAS44 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 44 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS44 \<1.6 = clinical remission, DAS44 ≤2.4 = low disease activity.
| participants | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 2 (N = 297) | 67 |
| Week 4 (N = 293) | 122 |
| Week 8 (N = 293) | 157 |
| Week 13 (N = 282) | 194 |
| Week 26 (N = 276) | 210 |
| Week 39 (N = 259) | 236 |
| Week 52 (N = 221) | 214 |
| Final on Therapy (N = 305) | 249 |
The PASS is defined as a symptom state that the participants consider acceptable.
| Participants | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Week 2 (N = 297) | 151 |
| Week 4 (N = 292) | 180 |
| Week 8 (N = 288) | 189 |
| Week 13 (N = 279) | 197 |
| Week 26 (N = 268) | 213 |
| Week 39 (N = 257) | 219 |
| Week 52 (N = 220) | 206 |
| Final on Therapy (N = 305) | 250 |
ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).
| participants | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 52 (N = 63, 63, 65) | 61 | 63 | 64 |
| Week 56 (N = 63, 63, 63) | 59 | 59 | 56 |
| Week 64 (N = 62, 61, 62) | 61 | 51 | 44 |
| Week 76 (N = 60, 55, 46) | 57 | 51 | 40 |
| Week 91 (N = 57, 50, 38) | 55 | 48 | 31 |
| Final on Therapy (N = 63, 63, 65) | 58 | 52 | 37 |
ACR50 response: greater than or equal to (≥) 50 percent (%) improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
| participants | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 52 (N = 63, 63, 65) | 58 | 61 | 62 |
| Week 56 (N = 63, 63, 63) | 55 | 58 | 48 |
| Week 64 (N = 62, 61, 62) | 59 | 47 | 33 |
| Week 76 (N = 60, 55, 46) | 54 | 48 | 33 |
| Week 91 (N = 57, 50, 38) | 48 | 45 | 29 |
| Final on Therapy (N = 63, 63, 65) | 50 | 47 | 32 |
ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
| participants | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 52 (N = 63, 63, 65) | 52 | 56 | 52 |
| Week 56 (N = 63, 63, 63) | 46 | 51 | 37 |
| Week 64 (N = 62, 61, 62) | 49 | 42 | 24 |
| Week 76 (N = 60, 55, 46) | 47 | 41 | 25 |
| Week 91 (N = 57, 50, 38) | 44 | 39 | 25 |
| Final on Therapy (N = 63, 63, 65) | 46 | 39 | 26 |
ACR90 response: greater than or equal to (≥) 90 percent (%) improvement in tender or swollen joint counts and 90% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
| participants | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 52 (N = 63, 63, 65) | 32 | 31 | 25 |
| Week 56 (N = 63, 63, 63) | 32 | 31 | 20 |
| Week 64 (N = 62, 61, 62) | 29 | 22 | 11 |
| Week 76 (N = 60, 55, 46) | 25 | 18 | 13 |
| Week 91 (N = 57, 50, 38) | 30 | 19 | 12 |
| Final on Therapy (N = 63, 63, 65) | 31 | 19 | 12 |
DAS44 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 44 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS44 \<1.6 = clinical remission, DAS44 ≤2.4 = low disease activity.
| Participants | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 52 (N = 63, 65, 65) | 60 | 62 | 60 |
| Week 56 (N = 63, 65, 63) | 52 | 52 | 47 |
| Week 64 (N = 62, 63, 60) | 54 | 44 | 25 |
| Week 76 (N = 60, 57, 46) | 51 | 42 | 24 |
| Week 91 (N = 57, 52, 38) | 48 | 39 | 23 |
| Final on Therapy (N = 63, 65, 65) | 51 | 40 | 24 |
DAS44 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 44 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS44 \<1.6 = clinical remission, DAS44 ≤2.4 = low disease activity.
| Participants | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 52 (N = 63, 65, 65) | 63 | 65 | 65 |
| Week 56 (N = 63, 65, 63) | 62 | 60 | 54 |
| Week 64 (N = 62, 63, 60) | 61 | 52 | 38 |
| Week 76 (N = 60, 57, 46) | 57 | 54 | 37 |
| Week 91 (N = 57, 52, 38) | 56 | 47 | 33 |
| Final on Therapy (N = 63, 65, 65) | 60 | 50 | 35 |
The composite measure of complete response over the last 3 months of Phase 2 was defined as: 1. DAS28 \<2.6 at the Week 76 and Week 91 visits and 2. No radiographic progression during Phase 2, defined as mean change from Week 52 in mTSS of ≤0.5. 3. Participant must achieve HAQ score ≤0.5 at Week 76 and 91 visits. HAQ is self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation.A subject had to satisfy all 3 criteria at thevisits to be defined as a responder
| Participants | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Number of Participants Achieving Complete Response (Using Disease Activity Score Based on a 28-joint Count, Modified Total Sharp Score, Health Assessment Questionnaire) | 36 | 19 | 7 |
Physician Global Assessment of Disease Activity was measured on a 0 to 100 Visual Analog Scale (VAS), with 0 = no disease activity and 100 = extreme disease activity.
| Units on a scale | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 52 (N = 63, 65, 65) | 5.0 ± 5.3 | 4.2 ± 4.9 | 6.3 ± 8.0 |
| Week 56 (N = 63, 65, 65) | 5.5 ± 6.2 | 7.7 ± 12.6 | 12.2 ± 15.1 |
| Week 64 (N = 62, 63, 62) | 6.0 ± 7.4 | 11.6 ± 16.7 | 23.6 ± 26.0 |
| Week 76 (N = 60, 57, 46) | 5.5 ± 7.1 | 9.0 ± 13.6 | 14.6 ± 18.1 |
| Week 91 (N = 57, 52, 38) | 5.8 ± 9.8 | 10.3 ± 16.8 | 15.9 ± 21.7 |
| Final on Therapy (N = 63, 65, 65) | 6.9 ± 10.8 | 16.7 ± 21.7 | 30.7 ± 28.4 |
Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = no disease activity and 100 = extreme disease activity
| Units on a scale | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 52 (N = 63, 65, 65) | 5.8 ± 6.3 | 5.7 ± 7.7 | 9.3 ± 14.1 |
| Week 56 (N = 63, 65, 65) | 10.3 ± 14.8 | 9.7 ± 16.3 | 17.3 ± 22.1 |
| Week 64 (N = 62, 63, 62) | 7.6 ± 9.1 | 17.8 ± 25.5 | 31.0 ± 31.4 |
| Week 76 (N = 60, 56, 46) | 8.9 ± 12.1 | 11.7 ± 17.9 | 18.3 ± 18.7 |
| Week 91 (N = 56, 52, 38) | 9.6 ± 14.1 | 12.3 ± 17.5 | 18.8 ± 25.7 |
| Final on Therapy (N = 63, 65, 65) | 11.1 ± 16.2 | 20.7 ± 25.9 | 37.1 ± 33.9 |
100-mm line (Visual Analog Scale) marked by the participant to measure their degree of pain over past 2-3 weeks. Range: 0 = no pain to 100 = pain as bad as it could be.
| mm | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 52 (N = 63, 65, 65) | 7.3 ± 7.7 | 6.9 ± 8.6 | 9.9 ± 14.8 |
| Week 56 (N = 63, 65, 65) | 10.9 ± 15.0 | 10.2 ± 16.9 | 18.8 ± 23.1 |
| Week 64 (N = 62, 63, 62) | 8.0 ± 9.8 | 18.0 ± 25.1 | 31.7 ± 31.3 |
| Week 76 (N = 60, 56, 46) | 9.8 ± 12.9 | 12.3 ± 19.2 | 17.6 ± 18.1 |
| Week 91 (N = 57, 52, 38) | 9.5 ± 12.7 | 13.3 ± 16.4 | 19.7 ± 26.1 |
| Final on Therapy (N = 63, 65, 65) | 11.4 ± 15.4 | 21.4 ± 24.8 | 37.8 ± 33.7 |
The PASS is defined as a symptom state that the subjects consider acceptable.
| Participants | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 52 (N = 61, 65, 64) | 57 | 64 | 61 |
| Week 56 (N = 63, 63, 64) | 57 | 58 | 53 |
| Week 64 (N = 61, 60, 60) | 58 | 51 | 42 |
| Week 76 (N = 60, 56, 45) | 57 | 48 | 38 |
| Week 91 (N = 57, 52, 38) | 52 | 46 | 33 |
| Final on Therapy (N = 63, 65, 65) | 56 | 50 | 38 |
mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
| Units on a scale | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Modified Total Sharp Score (mTSS) at Week 52 | 8.4 ± 13.5 | 8.4 ± 15.1 | 8.6 ± 12.8 |
mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
| Units on a scale | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 91 (N = 51, 45, 30) | 0.0 ± 0.16 | 0.0 ± 0.17 | 0.5 ± 0.21 |
| Final on Therapy (N = 58, 56, 49) | 0.1 ± 0.14 | -0.0 ± 0.15 | 0.4 ± 0.16 |
WPAI: 6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw (0-10) scores are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
| units on a scale | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Work Productivity and Activity Impairment (WPAI) Questionnaire: Percent Work Time Missed in the Past 7 Days Due to Problem | 0.2 ± 1.2 | 0.1 ± 0.6 | 0.0 ± 0.0 |
WPAI is a 6 question participant rated questionnaire determined the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores = greater impairment and less productivity. The raw (0-10) scores were converted to percent (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
| Units on a scale | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 64 (N = 30, 44, 26) | 1.9 ± 2.78 | 2.6 ± 2.29 | 6.1 ± 3.04 |
| Week 76 (N = 28, 33, 18) | -0.1 ± 2.38 | 2.9 ± 2.19 | 2.6 ± 3.09 |
| Week 91 (N = 29, 32, 14) | 4.4 ± 3.78 | 4.0 ± 3.63 | 7.0 ± 5.79 |
| Final on Therapy (N = 34, 48, 29) | 3.6 ± 3.65 | 5.3 ± 3.07 | 10.2 ± 4.06 |
WPAI: 6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw (0-10) scores are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
| units on a scale | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| WPAI Questionnaire: Percent Impairment While Working in the Past 7 Days Due to Problem | 6.2 ± 9.2 | 8.9 ± 15.5 | 14.2 ± 17.9 |
WPAI: 6 question participant rated questionnaire determined the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores = greater impairment and less productivity. The raw (0-10) scores were converted to percent (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
| Units on a scale | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 64 (N = 37, 49, 31) | -2.5 ± 3.57 | 9.6 ± 3.16 | 18.2 ± 3.96 |
| Week 76 (N = 38, 38, 23) | -0.6 ± 2.16 | 2.3 ± 2.01 | 12.2 ± 2.54 |
| Week 91 (N = 37, 35, 18) | 1.8 ± 3.16 | 8.6 ± 3.06 | 18.4 ± 4.23 |
| Final on Therapy (N = 45, 50, 40) | 1.1 ± 3.51 | 11.1 ± 3.10 | 19.9 ± 3.76 |
WPAI: 6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw (0-10) scores are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
| units on a scale | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| WPAI Questionnaire: Percent Overall Work Impairment in the Past 7 Days Due to Problem | 5.3 ± 9.8 | 6.7 ± 15.0 | 9.2 ± 12.8 |
WPAI: 6 question participant rated questionnaire determined the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores = greater impairment and less productivity. The raw (0-10) scores were converted to percent (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
| Units on a scale | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 64 (N = 29, 43, 25) | 0.1 ± 4.49 | 11.5 ± 3.75 | 22.4 ± 2.01 |
| Week 76 (N = 27, 30, 18) | -0.9 ± 2.40 | 2.6 ± 2.18 | 16.6 ± 2.95 |
| Week 91 (N = 28, 30, 13) | 5.4 ± 3.98 | 9.5 ± 3.74 | 22.0 ± 5.75 |
| Final on Therapy (N = 34, 48, 28) | 4.4 ± 4.32 | 13.3 ± 3.60 | 25.1 ± 4.84 |
WPAI: 6 question participant rated questionnaire to determine the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. The raw (0-10) scores are converted to percents (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
| Units on a scale | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| WPAI Questionnaire: Percent Activity Impairment in the Past 7 Days Due to Problem | 8.6 ± 11.0 | 10.0 ± 15.9 | 16.8 ± 20.0 |
WPAI: 6 question participant rated questionnaire determined the degree to which rheumatoid arthritis affected work productivity while at work and affected activities outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores = greater impairment and less productivity. The raw (0-10) scores were converted to percent (the variable is named "Percent impairment While Working") and as such range from 0 to 100.
| Units on a scale | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) |
|---|---|---|---|
| Week 64 (N = 56, 60, 57) | -0.5 ± 3.21 | 9.9 ± 3.10 | 19.1 ± 3.18 |
| Week 76 (N = 57, 55, 41) | 2.9 ± 2.94 | 7.1 ± 2.96 | 13.9 ± 3.35 |
| Week 91 (N = 53, 49, 37) | -1.8 ± 2.83 | 7.3 ± 2.87 | 17.9 ± 3.20 |
| Final on Therapy (N = 60, 64, 64) | -0.9 ± 3.24 | 12.2 ± 3.13 | 24.2 ± 3.16 |
Collected over Screening to Week 117 (Phase 1, 2, and 3 data). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| ETN 50 QW + MTX (Phase 1) | — | 28/306 (9.2%) | 130/306 (42.5%) |
| E25 + MTX (Phase 2) | — | 3/63 (4.8%) | 10/63 (15.9%) |
| MTX + PBO (Phase 2) | — | 2/65 (3.1%) | 8/65 (12.3%) |
| Placebo (PBO) (Phase 2) | — | 2/65 (3.1%) | 11/65 (16.9%) |
| E25+MTX (Phase 3) | — | 0/53 (0%) | 13/53 (24.5%) |
| MTX (Phase 3) | — | 0/46 (0%) | 8/46 (17.4%) |
| Placebo (PBO) (Phase 3) | — | 2/32 (6.3%) | 4/32 (12.5%) |
| Event | ETN 50 QW + MTX (Phase 1) | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) | E25+MTX (Phase 3) | MTX (Phase 3) | Placebo (PBO) (Phase 3) |
|---|---|---|---|---|---|---|---|
| Oral infectionInfections and infestations | 0/306 | 0/63 | 0/65 | 0/65 | 0/53 | 0/46 | 1/32 |
| VasculitisVascular disorders | 0/306 | 0/63 | 0/65 | 0/65 | 0/53 | 0/46 | 1/32 |
| PericarditisCardiac disorders | 0/306 | 1/63 | 0/65 | 0/65 | 0/53 | 0/46 | 0/32 |
| Ear canal stenosis postoperativeEar and labyrinth disorders | 0/306 | 1/63 | 0/65 | 0/65 | 0/53 | 0/46 | 0/32 |
| Bacterial pyelonephritisInfections and infestations | 0/306 | 1/63 | 0/65 | 0/65 | 0/53 | 0/46 | 0/32 |
| CystoceleReproductive system and breast disorders | 0/306 | 1/63 | 0/65 | 0/65 | 0/53 | 0/46 | 0/32 |
| Anal FissureGastrointestinal disorders | 0/306 | 0/63 | 0/65 | 1/65 | 0/53 | 0/46 | 0/32 |
| Femoral neck fractureInjury, poisoning and procedural complications | 0/306 | 0/63 | 1/65 | 0/65 | 0/53 | 0/46 | 0/32 |
| Rheumatoid arthritisMusculoskeletal and connective tissue disorders | 0/306 | 0/63 | 0/65 | 1/65 | 0/53 | 0/46 | 0/32 |
| HeadacheNervous system disorders | 1/306 | 0/63 | 1/65 | 0/65 | 0/53 | 0/46 | 0/32 |
| Event | ETN 50 QW + MTX (Phase 1) | E25 + MTX (Phase 2) | MTX + PBO (Phase 2) | Placebo (PBO) (Phase 2) | E25+MTX (Phase 3) | MTX (Phase 3) | Placebo (PBO) (Phase 3) |
|---|---|---|---|---|---|---|---|
| Rheumatoid arthritisMusculoskeletal and connective tissue disorders | 0/306 | 2/63 | 2/65 | 6/65 | 10/53 | 7/46 | 1/32 |
| NauseaGastrointestinal disorders | 39/306 | 0/63 | 0/65 | 0/65 | 0/53 | 0/46 | 0/32 |
| NasopharyngitisInfections and infestations | 39/306 | 5/63 | 3/65 | 3/65 | 3/53 | 0/46 | 1/32 |
| HeadacheNervous system disorders | 20/306 | 0/63 | 0/65 | 0/65 | 0/53 | 0/46 | 0/32 |
| Upper Respiratory Tract InfectionInfections and infestations | 17/306 | 4/63 | 3/65 | 3/65 | 0/53 | 0/46 | 0/32 |
| Urinary Tract InfectionInfections and infestations | 0/306 | 0/63 | 0/65 | 0/65 | 0/53 | 1/46 | 2/32 |
| Injection site reactionGeneral disorders | 19/306 | 0/63 | 0/65 | 0/65 | 0/53 | 0/46 | 0/32 |
| CoughRespiratory, thoracic and mediastinal disorders | 18/306 | 0/63 | 0/65 | 0/65 | 0/53 | 0/46 | 0/32 |
| Injection site ErythemaGeneral disorders | 17/306 | 0/63 | 0/65 | 0/65 | 0/53 | 0/46 | 0/32 |
| Alanine Aminotransferase IncreasedInvestigations | 17/306 | 0/63 | 0/65 | 0/65 | 0/53 | 0/46 | 0/32 |
A total of 306 participants were enrolled in the study (Phase 1). Out of the 306 participants, 193 were eligible and were randomized at a ratio of 1:1:1 to Phase 2 study. Of the 193 participants from Phase 2, a total of 131 participants were eligible and were randomized to Phase 3 study.
| Age, Continuous(Years) | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Mean | 49.94 ± 13.70 |
| Sex: Female, Male(Participants) | ETN 50 QW + MTX (Phase 1) |
|---|---|
| Female | 213 |
| Male | 93 |
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