TING-YUAN LANLee, Tai-JuTai-JuLeeChang, Ting-WeiTing-WeiChangTAI-CHUNG TSENGLai, Pei-HsinqPei-HsinqLaiCheng, Chiao-FengChiao-FengChengKao, Jui-HungJui-HungKaoLin, Kuan-YenKuan-YenLinPai, Shao-YuShao-YuPaiCHENG-HAN WUWang, Kung-YuKung-YuWangWEI-YUNG LOHuang, Shang-ChinShang-ChinHuangCHIEH-YU SHENLu, Cheng-HsunCheng-HsunLuYang, Hung-ChihHung-ChihYangSONG-CHOU HSIEHKO-JEN LI2025-12-162025-12-162025-12-01https://scholars.lib.ntu.edu.tw/handle/123456789/734670HBV 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. 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. 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. 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.enAsianJAK inhibitorsTNF inhibitorchronic hepatitis B virus infectionhepatitis B virushepatitis B virus reactivationhepatitis B virus seroconversionresolved hepatitis B virus infectionrheumatoid arthritisrituximab[SDGs]SDG3journal article10.1093/rheumatology/keaf41940794751