A Multicenter, Randomized, Double-Period, Double − Blind Study to Determine the Optimal Protocol for Treatment Initiation With Methotrexate and Adalimumab Combination Therapy in Patients With Early Rheumatoid Arthritis (OPTIMA)

Trial Information

A Multicenter, Randomized, Double-Period, Double − Blind Study to Determine the Optimal Protocol for Treatment Initiation With Methotrexate and Adalimumab Combination Therapy in Patients With Early Rheumatoid Arthritis (OPTIMA)

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.