Renal function–adjusted initial JAK inhibitor dosing and outcomes in rheumatoid arthritis: from the ANSWER cohort study
9 affiliations
- 1Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, 1-14-1 Mihara-dai, Minami-ku, Sakai, Osaka 590-0197 Japan
- 2Department of Health Information Management, Kurashiki Sweet Hospital, Kurashiki, Okayama Japan
- 3Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- 4Department of Clinical Immunology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
- 5Department of Orthopaedic Surgery, Faculty of Medicine, Graduate School of Medicine, The University of Osaka, Suita, Osaka Japan
- 6Department of Sports Medical Biomechanics, Faculty of Medicine, Graduate School of Medicine, The University of Osaka, Suita, Osaka Japan
- 7Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Hyogo Japan
- 8First Department of Internal Medicine, Kansai Medical University, Hirakata, Osaka Japan
- 9Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University, Takatsuki, Osaka Japan
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.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10067-026-08448-6.
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BibTeX
@article{tomita2026renal,
title = {{Renal function–adjusted initial JAK inhibitor dosing and outcomes in rheumatoid arthritis: from the ANSWER cohort study}},
author = {Daisuke Tomita and Yuji Nozaki and Rika Fukuda and Yumi Morimoto and Hirotaka Yamazawa and Kaori Ishimura and Chisato Ashida and Tetsu Itami and Toshihiko Shiga and Wataru Yamamoto and Koichi Murata and Hideo Onizawa and Motomu Hashimoto and Masao Katsushima and Kosuke Ebina and Iku Shirasugi and Yo Ueda and Yonsu Son and Naofumi Yoshida and Tohru Takeuchi and Shogo Matsuda and Koji Kinoshita},
journal = {Clinical Rheumatology},
year = {2026},
month = sep,
doi = {10.1007/s10067-026-08448-6},
url = {https://doi.org/10.1007/s10067-026-08448-6},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Renal function–adjusted initial JAK inhibitor dosing and outcomes in rheumatoid arthritis: from the ANSWER cohort study
AU - Daisuke Tomita
AU - Yuji Nozaki
AU - Rika Fukuda
AU - Yumi Morimoto
AU - Hirotaka Yamazawa
AU - Kaori Ishimura
AU - Chisato Ashida
AU - Tetsu Itami
AU - Toshihiko Shiga
AU - Wataru Yamamoto
AU - Koichi Murata
AU - Hideo Onizawa
AU - Motomu Hashimoto
AU - Masao Katsushima
AU - Kosuke Ebina
AU - Iku Shirasugi
AU - Yo Ueda
AU - Yonsu Son
AU - Naofumi Yoshida
AU - Tohru Takeuchi
AU - Shogo Matsuda
AU - Koji Kinoshita
PY - 2026
DA - 2026/09/29
JO - Clinical Rheumatology
DO - 10.1007/s10067-026-08448-6
UR - https://doi.org/10.1007/s10067-026-08448-6
AB - 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. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10067-026-08448-6.
SN - 0770-3198
SN - 1434-9949
ER -