The Relationship Between TNF‐α Inhibitor Potency and HBV Reactivation in Patients With Rheumatic Disorders

ABSTRACT Background Rheumatologic patients who test positive for hepatitis B surface antigen (HBsAg) or core antibody (HBcAb) are at risk of HBV reactivation when treated with TNF‐α inhibitors. The effect of TNF‐α inhibitor potency on this risk remains unclear, despite guidelines advising potency‐based risk stratification. This study examines how TNF‐α inhibitor potency influences the risk of HBV reactivation. Methods From January 2008 to June 2023, 711 new TNF‐α inhibitor users with rheumatic diseases were identified, including 39 HBsAg+ patients with antiviral prophylaxis, 72 HBsAg+ patients without antiviral prophylaxis, and 600 HBsAg−/HBcAb+ patients without prophylaxis. A Cox proportional hazards model assessed factors associated with HBV reactivation. Results Over 2526 person‐years of follow‐up, HBsAg+ patients without antiviral prophylaxis had the highest HBV reactivation rate at 104.1 per 1000 person‐years, followed by HBsAg−/HBcAb+ patients at 12.9, and HBsAg+ patients with antiviral prophylaxis at 12.6 per 1000 person‐years. Multivariate Cox regression revealed that high‐potency TNF‐α inhibitors significantly increased HBV reactivation risk in HBsAg+ patients without antiviral prophylaxis (aHR 3.24, 95% CI: 1.09–9.67, p = 0.04). Adalimumab had a higher reactivation risk compared to etanercept (aHR 3.23, 95% CI: 1.02–10.17, p = 0.04), followed by golimumab (aHR 3.27, 95% CI: 0.91–11.64, p = 0.07). For HBsAg−/HBcAb+ patients, TNF‐α inhibitor potency did not significantly impact HBV reactivation risk; instead, age over 65 was the only significant risk factor (aHR 3.37, 95% CI: 1.30–8.70, p = 0.01). Conclusion High‐potency TNF‐α inhibitors significantly increase HBV reactivation risk in HBsAg+ patients, while HBsAg−/HBcAb+ patients have a uniformly low risk across all inhibitors.