Herpes Zoster in Patients Treated with JAK Inhibitors for Immune-Mediated Inflammatory Diseases: Incidence, Associated Factors and Vaccination Uptake in a Real-World Cohort

Background/Objectives: This study aimed to determine the incidence of herpes zoster (HZ) and risk factors associated with its occurrence in patients receiving Janus kinase inhibitors (JAKis) for immune-mediated inflammatory diseases (IMIDs), while evaluating preventive strategies and zoster vaccine uptake. Methods: We conducted a retrospective single-center cohort study including patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease, atopic dermatitis and alopecia areata treated with upadacitinib, baricitinib or tofacitinib. The primary outcome was incident HZ during JAKi exposure. Incidence rates (IRs) were calculated per 100 person-years (PY) and Cox regression identified factors associated with HZ. Results: A total of 292 patients contributed 565.5 PY of JAKi exposure. During follow-up, 23 patients (7.9%) developed HZ, corresponding to an overall IR of 4.07/100 PY (95% CI 2.40–5.73). Incidence rates were numerically lower with upadacitinib and varied across disease groups; differences were not statistically significant. Diabetes mellitus (HR 3.05, 95% CI 1.28–7.29) and chronic kidney disease (HR 3.24, 95% CI 1.17–8.95) were independently associated with HZ. Herpes simplex infection requiring systemic antiviral therapy was more frequent among patients who developed HZ. Recombinant zoster vaccine (RZV) uptake was low (9.9%), but higher among patients evaluated in a dedicated infectious risk consultation. No HZ events were observed among RZV-vaccinated patients. Although six HZ events (26.1%) were severe, all cases resolved completely. Conclusions: HZ remains a relevant complication of JAKi therapy across IMIDs. Diabetes mellitus and chronic kidney disease may help identify higher-risk patients, while structured infectious risk assessment could improve vaccine uptake.