Conditions: Rheumatoid Arthritis
Keywords: Early Rheumatoid Arthritis Tumor Necrosis Factor Optimization
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1032
Healthy volunteers: no

Brief summary:
This study compared the safety and efficacy of combination therapy with adalimumab plus methotrexate (MTX) to that of MTX monotherapy (i.e., placebo plus MTX) in subjects with early rheumatoid arthritis (RA).

Detailed description:
This was a 78-week, multicenter, randomized, double-blind, double-treatment period study designed to compare the safety and efficacy of adalimumab and MTX with placebo and MTX in subjects with early RA. Subjects were randomized to receive adalimumab 40 mg every other week (eow) or placebo subcutaneous injections in combination with orally administered MTX for 26 weeks (Period 1). All subjects in all arms received open-label MTX weekly throughout the study (both Period 1 and Period 2).

At Weeks 22 and 26, subjects were assessed for achievement of low disease activity, defined as a DAS28 score below 3.2. DAS28 is a measure of RA disease activity calculated using the number of tender and swollen joints (out of a total of 28), C-reactive protein level (CRP, a blood marker of inflammation), and the patient's global assessment of disease activity (indicated by marking a 10 cm line between very good and very bad). Subjects who achieved low disease activity at Week 22 and 26 in the adalimumab arm at the end of Period 1 were randomized to receive MTX monotherapy (placebo and MTX) or combination therapy (adalimumab and MTX) in a 1:1 ratio for the duration of Period 2 (52 weeks, i.e., to Week 78 of the study). Subjects achieving low disease activity at Week 22 and 26 in the placebo arm (MTX monotherapy) at the end of Period 1 continued to receive MTX monotherapy (and placebo injections in a blinded fashion) for the duration of Period 2. Subjects failing to achieve low disease activity at Week 22 and 26 at the end of Period 1 received open-label combination therapy during Period 2 regardless of treatment assignment in Period 1.

Arms:
arm 1: Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2 arm 2: Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2 arm 3: Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA + MTX during Period 2 arm 4: Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2 arm 5: Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2.

Interventions: intervention 1: adalimumab intervention 2: methotrexate intervention 3: placebo
Intervention descriptions: intervention 1: Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow) intervention 2: Methotrexate 2.5 mg tablets administered orally once a week starting at 7.5 mg/week with dose escalation (weekly or every other week) by 2.5 mg intervals to 20 mg/week. intervention 3: Placebo for adalimumab 0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)

Protocol document: