Temporal Patterns of Outcomes After DMARD Tapering or Withdrawal in Rheumatoid Arthritis With Sustained Disease Control: A Systematic Review and Meta-Analysis

Rheumatoid arthritis (RA) requires lifelong treatment with disease-modifying antirheumatic drugs (DMARDs). In patients with sustained disease control, DMARD de-escalation has been proposed to lessen treatment burden, but its efficacy and safety remain elusive. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating DMARD tapering or withdrawal in controlled RA. PubMed, Embase, and the Cochrane Library were searched to January 16, 2026. The primary outcome was disease flare, and secondary outcomes included radiographic progression and adverse events (AEs). Risk ratios (RRs) were pooled using Mantel–Haenszel models. Prespecified subgroup analyses were conducted by DMARD class and follow-up duration. In total, 27 publications comprising 5262 participants were included. Any DMARD tapering increased flare risk overall (RR 1.56, 95% CI 1.26–1.98), mainly driven by the biologic DMARD (bDMARD) subgroup, with increased flare risk observed < 9 months (RR 1.61, 95% CI 1.13–2.31), but not at longer follow-up (> 9 months). In contrast, any DMARD withdrawal substantially increased flare risk (RR 2.23, 95% CI 1.83–2.94), primarily driven by the bDMARD subgroup across all follow-up durations (< 9 months, 9–18 months, and > 18 months). Both tapering (weak evidence) and withdrawal (strong evidence) promoted radiographic progression at 9–18 months and > 18 months. Neither tapering nor withdrawal reduced AEs. In conclusion, DMARD tapering, particularly of bDMARDs, should be considered cautiously in controlled RA because of the increased flare risk, possible radiographic progression, without clear reduction in AEs. DMARD withdrawal should be generally avoided whenever possible. Trial Registration: CRD420251066774 (PROSPERO). © 2026 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.