Temporal Patterns of Outcomes After DMARD Tapering or Withdrawal in Rheumatoid Arthritis With Sustained Disease Control: A Systematic Review and Meta-Analysis
In brief
Stopping rheumatoid arthritis drugs more than doubles flares; tapering raises risk 56%
Across 27 publications involving 5,262 people with controlled rheumatoid arthritis, stopping disease-modifying drugs more than doubled flare risk, while tapering raised it by 56%; the increased risk was driven mainly by biologic drugs. Both strategies showed signs of worsening joint damage, and neither reduced adverse events, making drug withdrawal especially difficult to justify.
- Journal
- Clinical and translational science (Q1)
- Published
- 1 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Xiaoyan Zhang, Rajan Kumar Pandey, Xi Luo, Zhongwei Xu
- PMID
- 42836514
- DOI
- 10.1111/cts.70740
Why clinicians should know about it
- Picked for Rheumatology (paper of the day, 7 October 2026): DMARD tapering increases flare risk in RA
Abstract
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).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.