Risk of disease flare and clinical reversibility following discontinuation versus dose reduction of biological DMARDs in Rheumatoid arthritis: A systematic review and meta-analysis

초록

Background: For patients with rheumatoid arthritis (RA) who achieve stable remission, a key clinical goal is the de-escalation of biological disease-modifying antirheumatic drugs (bDMARDs). However, the best approach-whether to completely discontinue treatment or to gradually reduce the dose-remains a topic of debate. This systematic review and meta-analysis aimed to compare the risks of flare, clinical reversibility, and radiographic safety associated with these two strategies. Methods: We conducted a search of PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published from inception until February 1, 2026. Eleven studies (including 10 RCTs and one 10-year extension study) involving 2861 patients were included. The primary outcome was the risk ratio (RR) of disease flare. Secondary outcomes included the re-treatment success rate (capture rate) and radiographic progression (vSHS). All analyses employed a random-effects model. The study protocol was registered in the PROSPERO database (Registration No CRD420261331554) Results: The pooled meta-analysis revealed that complete discontinuation of bDMARDs significantly increases the risk of flare compared to dose reduction or maintenance strategies (Pooled RR: 2.13; 95% CI: 1.74-2.61; P < 0.00001). Subgroup analysis based on disease duration indicated a significant interaction (P = 0.007); the risk of flare was lower in patients with early RA (<2 years; RR 1.62; 95% CI: 1.25-2.10) compared to those with established RA (RR 2.31; 95% CI: 1.89-2.82). Despite the increased flare risk, the pooled capture rate upon re-initiating therapy was 87.5% (95% CI: 82.4-91.6), with clinical recovery achieved within a median of 12.4 weeks. Radiographic progression was minimal and primarily driven by cumulative disease activity during flares rather than the tapering strategy itself. No significant publication bias was detected (Egger's test, P = 0.456). Conclusion: Gradual dose reduction is a safer initial de-escalation strategy than complete discontinuation for maintaining remission in RA. Although stopping bDMARDs more than doubles the risk of flare, the clinical consequences are largely reversible. A stepwise tapering approach, supported by strict monitoring and immediate re-treatment protocols, should be prioritized to balance treatment-free remission with structural safety.

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