Maintenance of response with conventional- or reduced-dose etanercept therapy or biologic free after induction of response with etanercept-methotrexate therapy in patients with moderately active rheumatoid arthritis participating in the PRESERVE study in Europe, Latin America, and Asia

Background: Active inflammation can result in potentially irreversible joint damage and functional disability early in the disease course in rheumatoid arthritis (RA).1 Earlier intervention with highly effective disease‐modifying antirheumatic drugs, including biologicals, helps patients achieve clinical remission or the lowest disease activity possible.2 Achievement of these therapeutic goals has not been well studied in patients with moderately active disease, who represent a large proportion of the RA population. Moreover, although interest is growing in the optimal use of biological agents, including induction‐maintenance strategies, biologic dose reduction or withdrawal (biologic free) in RA has not yet been assessed in a single controlled study. Objective: To compare the impact of continuing etanercept 50 mg QW with methotrexate (ETN50/MTX), reducing ETN from 50 mg to 25 mg QW with MTX (ETN25/MTX), and withdrawing ETN and providing MTX alone over 52 weeks after low disease activity (LDA) was sustained during an induction period with ETN50/MTX therapy in moderate RA patients enrolled in the PRESERVE study in understudied Eastern European, Latin American, and Asian countries (Taiwan, Chile, Colombia, Mexico, Czech Republic, Hungary, Serbia, Poland, and Russia). Methods: Patients with active RA [3.2 < DAS28 (ESR) 5.1] despite MTX therapy received ETN50/MTX in a 36‐week open‐label period; those achieving sustained DAS28 LDA (DAS28 3.2, avg week 12‐36 + at week 36) were randomized to ETN50/MTX, ETN25/ MTX, or MTX and evaluated in a subsequent 52‐week double‐blind period. The same MTX dose was maintained throughout (15‐25 mg). Results: Analyses included 491/388 patients in the open‐label/randomized periods. The percentage of patients achieving DAS28 LDA at week 88 was significantly higher with ETN50/MTX (82.7%) and E25/M (81.3%) than with MTX (50.4%; P < 0.0001). Significantly more patients in the ETN/MTX groups versus the biologic‐free group also achieved remission, ACR 20/50/70 responses, and a normal HAQ score (0.5) (P < 0.05; Table). Conclusions: The PRESERVE study is the first to assess the induction of therapeutic response with conventional‐dose biologic/MTX therapy (ETN50/MTX) and the subsequent (Table presented) maintenance of response with continued conventional‐dose or reduced‐dose (ETN25/MTX) therapy or biologic free on optimal background MTX in patients with moderately active RA despite MTX treatment. In this multinational subpopulation, patients receiving conventional‐ or reduced‐dose ETN/MTX were significantly more likely to maintain DAS28 LDA and other clinical/functional benefits over 52 weeks, after a 36‐week LDA induction, than those who were biologic free receiving MTX monotherapy.