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

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.