Clinical rheumatology · 2026
Renal function-adjusted initial JAK inhibitor dosing and outcomes in rheumatoid arthritis: from the ANSWER cohort study.
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Tomita Daisuke, Nozaki Yuji, Fukuda Rika, Morimoto Yumi, Yamazawa Hirotaka, Ishimura Kaori, Ashida Chisato, Itami Tetsu, Shiga Toshihiko, Yamamoto Wataru, Murata Koichi, Onizawa Hideo, Hashimoto Motomu, Katsushima Masao, Ebina Kosuke, Shirasugi Iku, Ueda Yo, Son Yonsu, Yoshida Naofumi, Takeuchi Tohru, Matsuda Shogo, Kinoshita Koji
Аннотация
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.
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.