FOR patients with rheumatoid arthritis (RA) with an inadequate response to Janus kinase inhibitors (JAKi), new research suggests that cycling to another JAKi may be more effective than switching to a biologic disease-modifying anti-rheumatic drug (bDMARD). Findings from the FIRST registry, published in RMD Open, highlight key treatment considerations for rheumatologists managing JAKi-resistant RA patients.
The study analyzed 434 RA patients who initiated JAKi treatment, with 138 (31.8%) classified as JAKi inadequate responders (JAKi-IR). These patients either failed to reach low disease activity within 26 weeks or required a treatment switch due to insufficient response. Researchers compared the efficacy and safety of switching to bDMARDs (n=45) versus cycling to another JAKi (n=31) over 26 weeks.
Results showed that patients who cycled to another JAKi experienced significant improvements in Clinical Disease Activity Index (CDAI) scores, with higher remission rates compared to those who switched to bDMARDs. Importantly, retention rates and adverse events were similar between the two groups, suggesting no additional safety concerns with JAKi cycling.
A trajectory analysis identified three distinct response patterns, with the “treatment response” group achieving rapid and sustained improvement when continuing with a different JAKi. Multiple logistic regression confirmed that cycling to another JAKi was a key predictor of positive treatment response.
These findings indicate that for patients with RA who do not respond adequately to initial JAKi therapy, staying within the JAK inhibitor class may offer better disease control compared to switching to a biologic DMARD. Further studies are needed to refine treatment strategies and optimize patient outcomes.
Reference: Miyazaki Y et al. Switching to biological DMARDs versus cycling among JAK inhibitors in patients with rheumatoid arthritis and with inadequate response to JAK inhibitors: from FIRST registry. RMD Open. 2025;11:e004987.
Anaya Malik | AMJ
