Seminars in arthritis and rheumatism · 2026
Comparative efficacy and safety of disease-modifying antirheumatic drugs tapering strategies in sustained-remission rheumatoid arthritis: Systematic review and network meta-analysis.
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Tandi Yosi Yohanes Putra, Syafa'atulloh Muhammad Yasir, Sigilipu Yitzchak Millenard, Utomo Garuda Nusantara Putra, Albarok Muhammad Abdir Rahman, Pramatya Stephen Hilkia, Hamijoyo Laniyati
Аннотация
BACKGROUND: International guidelines permit tapering disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) in sustained remission, but the de-escalation strategy with the lowest risk of flare remains unknown. Therefore, this study aimed to compare and rank flare risk across DMARD de-escalation strategies to guide more specific clinical decisions.
METHODS: We performed a systematic review and a frequentist random-effects network meta-analysis (NMA) of clinical studies, evaluating DMARD tapering in adults with RA in remission (≥6 months). The primary network compared maintenance therapy (N0), simultaneous dose reduction of cDMARDs and bDMARDs (N1), discontinuation of bDMARDs while continuing cDMARDs (N3), and dose reduction of bDMARDs while continuing cDMARDs (N4). Flare risk was pooled as RR (95% CI) using a consistency model, with ranking by P-scores. Assessments of risk of bias, network inconsistency, and confidence in network estimates using CINeMA, as well as sensitivity analysis including complete DMARD withdrawal (N2), were also conducted.
RESULTS: nineteen studies involving 3115 participants were included. Overall, tapering DMARDs increased the risk of flares compared with continued therapy (RR 1.94; 95%CI: 1.30-2.89). The primary NMA showed that tapering bDMARDs while continuing cDMARDs (N4) had the most favourable flare profile among the evaluated de-escalation strategies and was closest to maintenance therapy (RR 1.17; 95%CI: 0.76-1.82). In contrast, discontinuation of bDMARDs while continuing cDMARDs (N3) increased flare risk compared to N0 (RR 3.06; 95% CI: 1.81-5.16), and compared to N4 (RR 2.61; 95% CI: 1.44-4.72). The order of strategies identified was N0 > N4 > N1 > N3. CINeMA confidence was high for N3 versus N0 and moderate for N4 versus N0.
CONCLUSIONS: Gradual bDMARD dose reduction while maintaining background cDMARD as backbone therapy showed the most favourable comparative flare profile, whereas bDMARD discontinuation was associated with a substantially higher flare risk.
METHODS: We performed a systematic review and a frequentist random-effects network meta-analysis (NMA) of clinical studies, evaluating DMARD tapering in adults with RA in remission (≥6 months). The primary network compared maintenance therapy (N0), simultaneous dose reduction of cDMARDs and bDMARDs (N1), discontinuation of bDMARDs while continuing cDMARDs (N3), and dose reduction of bDMARDs while continuing cDMARDs (N4). Flare risk was pooled as RR (95% CI) using a consistency model, with ranking by P-scores. Assessments of risk of bias, network inconsistency, and confidence in network estimates using CINeMA, as well as sensitivity analysis including complete DMARD withdrawal (N2), were also conducted.
RESULTS: nineteen studies involving 3115 participants were included. Overall, tapering DMARDs increased the risk of flares compared with continued therapy (RR 1.94; 95%CI: 1.30-2.89). The primary NMA showed that tapering bDMARDs while continuing cDMARDs (N4) had the most favourable flare profile among the evaluated de-escalation strategies and was closest to maintenance therapy (RR 1.17; 95%CI: 0.76-1.82). In contrast, discontinuation of bDMARDs while continuing cDMARDs (N3) increased flare risk compared to N0 (RR 3.06; 95% CI: 1.81-5.16), and compared to N4 (RR 2.61; 95% CI: 1.44-4.72). The order of strategies identified was N0 > N4 > N1 > N3. CINeMA confidence was high for N3 versus N0 and moderate for N4 versus N0.
CONCLUSIONS: Gradual bDMARD dose reduction while maintaining background cDMARD as backbone therapy showed the most favourable comparative flare profile, whereas bDMARD discontinuation was associated with a substantially higher flare risk.