Non-negligible risk of HBV reactivation among rheumatoid arthritis patients receiving JAK inhibitors: bridging the evidence gap

OBJECTIVE: HBV reactivation is a critical concern for patients with autoimmune disease undergoing immunosuppressive therapy. Despite data on HBV reactivation risks associated with biologics, the impact of the new targeted immunosuppressive agents-Janus kinase inhibitors (JAKis)-remains unclear. This study aimed to evaluate the risk of HBV reactivation among patients with RA treated with JAKis, compared with those receiving TNF inhibitors (TNFis) or rituximab. METHOD: We conducted a retrospective analysis of patients with RA treated at the National Taiwan University Hospital from 2015 to 2023. Patients with available baseline HBV status [HBsAg, hepatitis B core antibody (anti-HBc), hepatitis B surface antibody (anti-HBs), HBV DNA] who received TNFis, rituximab, or JAKis (tofacitinib, baricitinib, upadacitinib) were included. The primary outcomes were hepatitis flare in HBsAg-positive patients and HBsAg seroreversion in HBsAg-negative/anti-HBc-positive patients. RESULTS: We included 35 HBsAg-positive patients and 339 patients with resolved HBV infection (HBsAg-negative/anti-HBc-positive). Among those with resolved HBV infection, the reactivation risk was low with TNFis (0.9%, 2.8/1000 person-years), and higher with rituximab (3.2%, 15.1/1000 person-years) and JAKis overall (2.9%, 10.3/1000 person-years). Among individual JAKis, upadacitinib had the highest incidence (6.5%, 42.8/1000 person-years), followed by baricitinib (4.7%, 19.2/1000 person-years), and tofacitinib (1.0%, 2.7/1000 person-years). Among HBsAg-positive patients, 50% of JAKi users developed a hepatitis flare, emphasizing the importance of vigilant monitoring and prophylaxis. CONCLUSION: Our findings reveal a non-negligible risk of HBV reactivation among RA patients receiving JAKi therapy, particularly with the more JAK1-selective JAKis. Larger registry or prospective studies are needed to validate these findings.