JAK Inhibitors and Herpes Zoster in UC: Genetic Insights for Safer Treatment Strategies

Aim: JAK inhibitors have significantly improved ulcerative colitis (UC) treatment, however, herpes zoster (HZ) remains a major safety concern. Previous studies have reported an increased HZ risk in rheumatoid arthritis patients with IL17RB and TOX3 mutations. This study investigates the genetic factors influencing HZ risk in UC patients treated with JAK inhibitors. Methods: Genetic analysis was performed to identify mutations in IL17RB and TOX3. Genetic associations were evaluated for age, sex, and concomitant immunosuppressive therapy. Results :Between January 2008 and September 2023, a total of 535 UC patients were followed up at our hospital, of whom 33 consented to genomic analysis. Additionally, 37 UC patients received JAK inhibitor treatments: tofacitinib (n=28), filgotinib (n=8), and upadacitinib (n=1). In patients treated with filgotinib, immunomodulators were continued. Among the 37 UC patients treated with JAK inhibitors, 7 (18.9%) developed HZ. Specifically, HZ occurred in 6 out of 28 patients (21.4%) receiving tofacitinib, none of the 8 patients receiving filgotinib, and the single patient receiving upadacitinib. Genetic analysis revealed that patients carrying the IL17RB mutation had a 4.5-fold increased risk of HZ, whereas no significant association was found between TOX3 mutations and HZ (p=0.58, not significant). Conclusion: Our findings highlight the importance of genetic screening for UC patients receiving JAK inhibitors. Additionally, filgotinib demonstrated a lower incidence of HZ compared to tofacitinib, even when used with immunomodulators.