Efficacy and safety of down-titration versus continuation strategies of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis with low disease activity or in remission: a systematic review and meta-analysis.

Objective. To evaluate the efficacy and safety of down titration (dose reduction/tapering) strategies compared with continuation of biological disease modifying anti rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who achieved and maintained low disease activity or remission. Methods. We searched the following electronic 'database up to March 2016: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and conference proceedings of the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR). Our meta analysis included randomized controlled trials (RCTs) of RA patients with low disease activity or in remission that compared down titration treatment with continuation treatment. Data on flare, defined as a 28 joint Disease Activity Score of >= 3.2, had to have been reported. Outcomes on efficacy or safe-' ty were collected. Results. Of 1136 references identified, five RCTs (total, 771 participants) were included. The incidence of disease relapse in the down titration and continuation groups was similar (risk ratio (RR)=1.14, 95% C1=0.88-1.49). There was no statistical difference in the number of serious adverse events (RR= 1.15, 95% C1=0.53-2.49). Withdrawals due to inefficacy or toxicity were similar between groups and no clinically meaningfid difference in efficacy outcomes was observed by continuation treatment. Conclusion. Our findings indicated that continuing a standard dose of biological DMARDs in patients with low disease activity conveyed no significant benefit as compared with down titration therapy, suggesting that a down titration strategy is as effective as a continuation strategy. Since the number of trials meeting the criteria for this meta analysis was relatively low, figure analyses with additional prospective RCTs are required to compare other biological agents and evaluate the long-term efficacy of these two strategies.