Outcomes of Tapering Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis: A Multicenter Randomized Noninferiority Trial

초록

Objective Evidence supporting tapering of biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients with rheumatoid arthritis (RA) with sustained low disease activity (LDA) remains limited. We evaluated the efficacy and safety of a structured b/tsDMARD-tapering strategy in patients with RA who had achieved sustained LDA. Methods In this 24-week, multicenter, randomized, open-label, noninferiority trial, patients with RA receiving stable-dose b/tsDMARDs and maintaining Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR)-defined LDA for at least six months were randomized to either stepwise dose tapering or dose continuation. The primary endpoint was maintenance of DAS28-ESR LDA at week 24. The noninferiority margin was prespecified as -10%. Secondary endpoints included disease activity measures, remission rates, patient-reported outcomes, quality of life, and adverse events. Results A total of 348 patients were randomized to the continuation group (n = 177) or tapering group (n = 171). In the per-protocol population, LDA was maintained in 89.6% and 88.2% of patients, respectively, with a risk difference of -1.43% (95% confidence interval -8.09 to 5.23), meeting the prespecified criterion for noninferiority. Similar findings were observed in the full analysis set. Most patients experiencing disease worsening regained LDA after protocol-guided treatment reescalation during follow-up without permanent treatment discontinuation. Most secondary outcomes were comparable between groups, although some disease activity measures favored continuation, including DAS28 using the C-reactive protein level at week 12 and DAS28-ESR and Simplified Disease Activity Index at week 24. Adverse events were uncommon in both groups. Conclusion In patients with RA with sustained LDA, structured b/tsDMARD tapering was noninferior to treatment continuation for maintaining disease control over 24 weeks.

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