Disease flares among early rheumatoid arthritis patients treated with continued methotrexate either alone or in combination with adalimumab (Humira)

Background/Purpose : Some rheumatoid arthritis (RA) patients (pts) may experience flares in their disease even after reaching stable low disease activity (sLDA), but the consequences of even temporary elevations in disease activity are poorly understood. The purpose of this analysis was to explore the rates of flares after reaching sLDA in pts treated to target with either methotrexate (MTX) monotherapy or adalimumab combination therapy (ADA+MTX). Methods : This post hoc analysis included pts from the randomized, double-blind, double-period OPTIMA1 trial achieving sLDA [DAS28(CRP) <3.2 at weeks (wks) 22 and 26] at the end of period 1 (P1). In P1, pts were randomized to receive ADA+MTX or placebo (PBO)+MTX for 26 wks. Pts on ADA+MTX achieving sLDA were randomized to receive PBO+MTX (ADA Withdrawal) or continue on ADA+MTX (ADA Continuation) for an additional 52 wks in period 2 (P2). Pts who achieved sLDA on PBO+MTX in P1 continued their treatment in P2 (MTX Continuation). Pts achieving sLDA in each treatment group were categorized based on whether they experienced a flare [change in DAS28(CRP) ≥0.6 at consecutive visits and DAS28(CRP) ≥3.2]; the proportion of pts experiencing flares and time to flare were assessed. For each group, mean change from wk 26 to wk 78 in disease activity [DAS28(CRP)], functional (HAQ-DI) and structural (mTSS) measures were analyzed. Results : In pts achieving sLDA at the end of P1, flare rates in P2 differed based on initial treatment assignment (ADA Continuation: 11.7% [11/94]; MTX Continuation: 22.4% [22/98]). Interestingly, flare rates in pts randomized to withdraw ADA in P2 (ADA Withdrawal: 25% [22/88]) were numerically similar to the MTX Continuation group. The mean time to flare was 193, 191, and 177 days in the ADA Withdrawal, ADA Continuation, and MTX Continuation groups, respectively. During P2, the mean DAS28(CRP) scores were predictably higher in pts who flared compared with those who did not across treatment groups. In pts experiencing flares in P2, disease activity and functional measures worsened from wk 26 to wk 78 as compared with pts without flares (Table). Of the individual DAS28(CRP) components, pt global assessment of disease activity (PtGA) showed the greatest worsening. There were small differences in radiographic progression between pts experiencing flares compared with pts without flares. Conclusion : In early RA pts achieving sLDA, flares were generally infrequent; however, they were more prevalent in pts receiving PBO+MTX compared with ADA+MTX. Flares were numerically associated with higher disease activity, functional deterioration, and higher PtGA, underscoring its impact on health-related quality of life and the importance of preventing flares as a therapeutic outcome.