Reasons-stratified treatment retention after JAK inhibitor discontinuation in rheumatoid arthritis: the ANSWER cohort study.

IF 4.7 2区医学 Q1 RHEUMATOLOGY

Rheumatology Pub Date : 2026-10-20 DOI:10.1093/rheumatology/keag587

Yuhei Fujisawa, Ryu Watanabe, Yuya Yano, Kosaku Murakami, Koichi Murata, Yuri Hiramatsu, Toru Takeuchi, Yuki Etani, Yasutaka Okita, Hideki Amuro, Hirotaka Yamada, Yo Ueda, Ryota Hara, Masaki Katayama, Yuji Nozaki, Tetsu Itami, Wataru Yamamoto, Ryuhei Ishihara, Masao Katsushima, Kazuo Fukumoto, Shinsuke Yamada, Tadashi Okano, Motomu Hashimoto

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引用次数: 0

Abstract

Objective: To compare the retention and disease activity trajectories of subsequent biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) after Janus kinase inhibitor (JAKi) discontinuation in patients with rheumatoid arthritis (RA).

Methods: We analysed 500 treatment courses (TCs) from the ANSWER cohort in which subsequent b/tsDMARDs were initiated after JAKi discontinuation. Subsequent treatments were classified as TNF inhibitors (TNFi), anti-IL-6 receptor antibodies (aIL-6R), CTLA4-Ig and JAKi. Drug retention was stratified by the reason for prior JAKi discontinuation and evaluated using Kaplan-Meier and multivariable Cox analyses. Changes in Clinical Disease Activity Index (CDAI) over 12 months were analysed using mixed-effects models for repeated measures.

Results: After prior JAKi discontinuation due to ineffectiveness, CTLA4-Ig was associated with a significantly higher risk of discontinuation due to ineffectiveness than subsequent JAKi (HR 2.83, 95% CI 1.20-6.70). Among TCs in which the prior JAKi was discontinued due to toxic adverse events (AEs), TNFi and aIL-6R were associated with lower risks of toxic AE-related discontinuation than JAKi. Overall CTLA4-Ig was associated with higher risks of discontinuation due to ineffectiveness (HR 2.57, 95% CI 1.46-4.54) and total discontinuation excluding non-toxic reasons and remission (HR 1.77, 95% CI 1.02-3.07). CDAI trajectories over 12 months did not differ significantly between treatment groups.

Conclusion: The optimal treatment strategy after JAKi discontinuation may depend on the reason for prior discontinuation. JAKi cycling, TNFi and aIL-6R may be reasonable after ineffectiveness, whereas after toxic AEs, TNFi and aIL-6R were associated with lower risks of subsequent toxic AE-related discontinuation than JAKi cycling.

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原因：类风湿性关节炎患者停用JAK抑制剂后继续分层治疗：ANSWER队列研究。

目的：比较类风湿性关节炎（RA）患者Janus激酶抑制剂（JAKi）停药后生物和靶向合成疾病改善抗风湿药物（b/tsDMARDs）的保留和疾病活动轨迹。方法：我们分析了来自ANSWER队列的500个疗程（tc），其中在JAKi停药后开始使用b/ tsdmard。后续治疗分为TNF抑制剂（TNFi）、抗il -6受体抗体（il - 6r）、CTLA4-Ig和JAKi。根据先前停用JAKi的原因对药物保留进行分层，并使用Kaplan-Meier和多变量Cox分析进行评估。使用重复测量的混合效应模型分析12个月内临床疾病活动指数（CDAI）的变化。结果：先前因JAKi无效而停药后，CTLA4-Ig与因JAKi无效而停药的风险显著高于随后的JAKi （HR 2.83, 95% CI 1.20-6.70）。在先前因毒性不良事件（ae）而停药的tc中，TNFi和aIL-6R与毒性ae相关停药的风险低于JAKi。总体而言，CTLA4-Ig因无效而停药的风险较高（HR 2.57, 95% CI 1.46-4.54），以及排除无毒原因和缓解的总停药风险较高（HR 1.77, 95% CI 1.02-3.07）。12个月以上的CDAI轨迹在治疗组之间没有显著差异。结论：JAKi停药后的最佳治疗策略可能取决于先前停药的原因。无效后，JAKi循环、TNFi和aIL-6R可能是合理的，而毒性ae后，TNFi和aIL-6R与随后毒性ae相关停药的风险低于JAKi循环。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Rheumatology 医学-风湿病学

CiteScore

9.40

自引率

7.30%

发文量

1091

审稿时长

2 months

期刊介绍： Rheumatology strives to support research and discovery by publishing the highest quality original scientific papers with a focus on basic, clinical and translational research. The journal’s subject areas cover a wide range of paediatric and adult rheumatological conditions from an international perspective. It is an official journal of the British Society for Rheumatology, published by Oxford University Press. Rheumatology publishes original articles, reviews, editorials, guidelines, concise reports, meta-analyses, original case reports, clinical vignettes, letters and matters arising from published material. The journal takes pride in serving the global rheumatology community, with a focus on high societal impact in the form of podcasts, videos and extended social media presence, and utilizing metrics such as Altmetric. Keep up to date by following the journal on Twitter @RheumJnl.