Renal function-adjusted initial JAK inhibitor dosing and outcomes in rheumatoid arthritis: from the ANSWER cohort study.

IF 2.7 3区医学 Q2 RHEUMATOLOGY

Clinical Rheumatology Pub Date : 2026-09-29 DOI:10.1007/s10067-026-08448-6

Daisuke Tomita, Yuji Nozaki, Rika Fukuda, Yumi Morimoto, Hirotaka Yamazawa, Kaori Ishimura, Chisato Ashida, Tetsu Itami, Toshihiko Shiga, Wataru Yamamoto, Koichi Murata, Hideo Onizawa, Motomu Hashimoto, Masao Katsushima, Kosuke Ebina, Iku Shirasugi, Yo Ueda, Yonsu Son, Naofumi Yoshida, Tohru Takeuchi, Shogo Matsuda, Koji Kinoshita

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引用次数: 0

Abstract

Introduction/objectives: To evaluate clinical effectiveness and treatment persistence after renal function-guided reduced-dose initiation of Janus kinase inhibitors (JAKis) in rheumatoid arthritis (RA).

Method: We analysed 368 adults initiating a JAKi in the ANSWER registry (2013-2023), classified as preserved renal function/standard dose (PR-Std; n = 246), preserved renal function/reduced dose (PR-Red; n = 68), or impaired renal function/reduced dose (IR-Red; n = 54). Outcomes were 6-month CDAI change, remission/LDA at days 84 and 168, and 12-month retention. IPTW addressed confounding; time-dependent Cox models evaluated dosing strategy × log(time + 1) interactions.

Results: Weighting improved covariate balance (standardised mean differences ≤ 0.20; most ≤ 0.10). Six-month CDAI improvement was similar across groups, and no between-group contrast in ΔCDAI at days 28, 56, 84, or 168 reached statistical significance. At Day 168, IPTW-weighted low disease activity rates were 58.5% in PR-Std, 66.9% in PR-Red, and 68.2% in IR-Red, while remission rates were 21.7%, 19.9%, and 21.1%, respectively. IPTW-weighted 12-month retention was 0.53, 0.67, and 0.44, respectively. Adverse-event-related discontinuation was not clearly higher with reduced-dose initiation.

Conclusions: Reduced-dose initiation showed no clear differences in 6-month CDAI outcomes or 12-month persistence versus standard-dose initiation; however, the modest reduced-dose sample sizes and wide CIs preclude excluding small but clinically meaningful differences. Because systematic safety outcomes were not captured, AE-related discontinuation should be interpreted only as a proxy for tolerability. Key Points • Renal function-guided reduced-dose initiation of JAK inhibitors showed no clear differences in 6-month CDAI outcomes compared with standard-dose initiation. • Remission and low disease activity rates at days 84 and 168 were broadly similar across dosing groups. • In patients with preserved renal function, reduced-dose initiation showed numerically higher 12-month retention, although absolute differences were modest.

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类风湿关节炎患者JAK抑制剂初始剂量和预后：来自ANSWER队列研究

目的：评价肾功能引导下小剂量启动Janus激酶抑制剂（JAKis）治疗类风湿性关节炎（RA）的临床疗效和治疗持久性。方法：我们分析了ANSWER登记处（2013-2023）中368名开始JAKi的成年人，分为保留肾功能/标准剂量（PR-Std, n = 246）、保留肾功能/减少剂量（PR-Red, n = 68）或肾功能受损/减少剂量（IR-Red, n = 54）。结果是6个月的CDAI改变，第84天和168天的缓解/LDA，以及12个月的保持。IPTW解决了混淆；时间依赖的Cox模型评估了给药策略× log（时间+ 1）相互作用。结果：加权改善了协变量平衡（标准化平均差异≤0.20，大多数≤0.10）。6个月的CDAI改善在各组之间相似，在ΔCDAI的28天、56天、84天或168天的组间对比没有统计学意义。在第168天，iptw加权的低疾病活动性在PR-Std组为58.5%，PR-Red组为66.9%，IR-Red组为68.2%，而缓解率分别为21.7%，19.9%和21.1%。iptw加权的12个月留存率分别为0.53、0.67和0.44。不良事件相关的停药并没有随着起始剂量的减少而明显增加。结论：与标准剂量起始相比，减少剂量起始在6个月CDAI结局或12个月持续性方面没有明显差异；然而，适度的减少剂量样本量和广泛的ci排除了微小但有临床意义的差异。由于系统安全性结果未被捕获，ae相关停药应仅被解释为耐受性的代表。•肾功能引导的JAK抑制剂低剂量起始治疗与标准剂量起始治疗相比，6个月CDAI结局无明显差异。•在第84天和168天，不同给药组的缓解率和低疾病活动率大致相似。•在保留肾功能的患者中，尽管绝对差异不大，但减少剂量的起始剂量在数字上显示出更高的12个月保留率。

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

Clinical Rheumatology 医学-风湿病学

CiteScore

6.90

自引率

2.90%

发文量

441

审稿时长

3 months

期刊介绍： Clinical Rheumatology is an international English-language journal devoted to publishing original clinical investigation and research in the general field of rheumatology with accent on clinical aspects at postgraduate level. The journal succeeds Acta Rheumatologica Belgica, originally founded in 1945 as the official journal of the Belgian Rheumatology Society. Clinical Rheumatology aims to cover all modern trends in clinical and experimental research as well as the management and evaluation of diagnostic and treatment procedures connected with the inflammatory, immunologic, metabolic, genetic and degenerative soft and hard connective tissue diseases.