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

Abstract Objective Hepatitis B virus (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 this new targeted immunosuppressive agents—Janus kinase inhibitors (JAKi) - remains unclear. This study aimed to evaluate the risk of HBV reactivation among rheumatoid arthritis (RA) patients treated with JAK inhibitors, compared with those receiving TNF inhibitors or rituximab. Method We conducted a retrospective analysis of RA patients treated at National Taiwan University Hospital from 2015 to 2023. Patients with available baseline HBV status (HBsAg, anti-HBc, anti-HBs, HBV DNA) who received TNF inhibitors, rituximab, or JAKi (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 TNF inhibitors (0.9%, 2.8/1,000 person-years), higher with rituximab (3.2%, 15.1/1,000 person-years) and JAKi overall (2.9%, 10.3/1,000 person-years). Among individual JAK inhibitors, upadacitinib had the highest incidence (6.5%, 42.8/1,000 person-years), followed by baricitinib (4.7%, 19.2/1,000 person-years), and tofacitinib (1.0%, 2.7/1,000 person-years). Among HBsAg-positive patients, 50% of JAKi users developed a hepatitis flare, emphasizing the importance of vigilant monitoring and prophylaxis. Conclusions Our findings reveal a non-negligible risk of HBV reactivation among RA patients receiving JAKi therapy, particularly with the more JAK1-selective JAKi. Larger registry or prospective studies are needed to validate these findings.