Study Evaluating Efficacy / Safety of Etanercept + Methotrexate Compared to Usual Treatment in Moderate RA Subjects
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT00706797
- Lead Sponsor
- Wyeth is now a wholly owned subsidiary of Pfizer
- Brief Summary
To assess comparative radiographic efficacy, clinical efficacy and safety of etanercept (ETN) + methotrexate (MTX) with usual disease-modifying anti-rheumatic drug (DMARD) treatment in subjects with moderate RA who were treated with MTX monotherapy, but continue to have moderate disease activity.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 141
- Meet the 1987 ACR Revised Criteria for Rheumatoid Arthritis.
- Documented evidence, confirmed by a blinded 3rd party assessor, of at least one erosion observed by X-ray at randomization based on X-ray taken at the screening visit.
- Have received MTX as stable dose for 28 days prior to the screening visit.
- Previous treatment with ETN, infliximab, adalimumab, other Tumor necrosis factor (TNF) -a inhibitors, anakinra or other biological agents.
- Receipt of any DMARD, other than MTX, within 28 days before screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Usual care methotrexate Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold). ETN + MTX etanercept (EnbrelTM) Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM). ETN + MTX methotrexate Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
- Primary Outcome Measures
Name Time Method Change From Baseline in Modified Total Sharp Score (TSS) at Week 52 Baseline, Week 52 Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 \[no narrowing\] to 168 \[high narrowing\]) plus (+) erosion score (range is from 0 \[no erosion\] to 280 \[high erosion\]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Erosions at Week 52 Baseline, Week 52 Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Change From Baseline in Joint Space Narrowing at Week 52 Baseline, Week 52 Joint space narrowing score (a component of the modified TSS) is a measure of change in joint health. Joint space narrowing score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Percentage of Participants Showing no Radiographic Progression (TSS Change <0.5) at Week 52 Baseline, Week 52, Last observation carried forward (LOCF) Radiographic non-progression determined based on TSS change \<0.5 using the dichotomous response Yes / No. The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Percentage of Participants Achieving >1.2 Improvement in Disease Activity Score Based on a 28-joint Count (DAS28) Baseline, Week 12, Week 24, and Week 52 Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and general health (GH) using Visual Analog Scale (VAS); range 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 square root (√) (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score \>5.1=higher disease activity; \<3.2=low disease activity; \<2.6=clinical remission. Achievement of \>1.2 improvement defined as decrease in DAS28 \>1.2 (change in DAS28 \< -1.2).
Percentage of Participants Achieving a Patient Acceptable Symptom State (PASS) Week 4, Week 12, Week 24, Week 40, Week 52 Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of pain they had during the last 48 hours.
Percentage of Participants Achieving Remission (DAS28 <2.60) Week 12, Week 24, and Week 52 Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score \>5.10=higher disease activity; \<3.20=low disease activity; \<2.60=clinical remission.
Percentage of Participants Achieving Low Disease Activity (DAS28 ≤3.20) Week 12, Week 24, and Week 52 Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score \>5.10=higher disease activity; \<3.20=low disease activity; \<2.60=clinical remission.
Percentage of Participants Achieving a >0.6 Disease Activity Score (DAS)28 Response Week 12, Week 24, and Week 52 Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and participant's assessment of general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score \>5.10=higher disease activity; \<3.20=low disease activity; \<2.60=clinical remission. DAS28 response of \>0.6 defined as decrease in DAS28 \>0.6 (change in DAS28 \< -0.6).
Percentage of Participants Achieving Moderate or Good Response on European League Against Rheumatism (EULAR) Response Criteria Week 12, Week 24, Week 52 Response to treatment assessed by EULAR response criteria. Participants were characterized as good, moderate, or non-responders based on both Disease Activity Score (DAS) level attained and change in DAS. Good response defined as \>1.2 improvement in DAS from Baseline and DAS attained during follow-up of ≤2.4. Non-responders = participants with improvement of ≤0.6 or participants with improvement of \>0.6 but ≤1.2 and DAS attained during follow-up of \>5.1. Remaining participants were classified as moderate. Scores of good and moderate were considered to have therapeutic response.
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response Week 12, Week 24, Week 52 American College of Rheumatology 20% (ACR20) response: responder = ≥ 20% improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.
Percentage of Participants With American College of Rheumatology 50% (ACR50) Response Week 12, Week 24, Week 52 American College of Rheumatology 50% (ACR50) response: responder = ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.
Percentage of Participants With American College of Rheumatology 70% (ACR70) Response Week 12, Week 24, Week 52 American College of Rheumatology 70% (ACR70) response: responder = ≥ 70% improvement in tender joint count; ≥ 70% improvement in swollen joint count; and ≥ 70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and erythrocyte sedimentation rate (ESR) . Subjects withdrawing early were non-responders.
Percentage of Participants With American College of Rheumatology 90% (ACR90) Response Week 12, Week 24, Week 52 American College of Rheumatology 90% (ACR 90) response: responder = ≥ 90% improvement in tender joint count; ≥ 90% improvement in swollen joint count; and ≥ 90% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.
Change From Baseline in Mean Daily Dose of Corticosteroids to Manage Flare-ups Across the 52-week Treatment Period Week 4, Week 12, Week 24, Week 40, Week 52 Mean daily dose of corticosteroids to manage flare-ups (temporary increases in corticosteroid dose or use of intra-articular steroids) during treatment period. Daily dose of equivalent prednisone derived in mg/day: oral corticosteroids: 5 mg of prednisone = 5 mg of prednisolone = 25 mg of cortisone = 20 mg of hydrocortisone = 4 mg of methylprednisolone = 4 mg of triamcinolone = 2mg of paramethasone = 0.75 mg of betamethasone = 0.75 of dexamethasone = 0.3 of cortivazol.
Percentage of Participants Achieving a Minimal Clinically Important Improvement (MCII) Week 12, Week 52 Participants were asked how their pain had been during the last 48 hours compared to baseline. Participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse-more pain.
Health Related Quality of Life: EuroQol-5D Health Index Baseline, Week 12, Week 24, and Week 52 EQ-5D is a self-administered questionnaire to assess health-related quality of life in 5 domains (mobility, self care, usual activities, pain or discomfort, and anxiety or depression). Scores from the 5 domains are used to calculate the Health State Profile Score as a single index value; range: 0.0 (death) to 1.0 (perfect health); higher scores indicate a better health state.
Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) Baseline, Week 12, Week 24, and Week 52 EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.