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

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.