Hepatitis B reactivation linked to tumor necrosis factor-α inhibitors in rheumatoid arthritis: a systematic review and meta-analysis

HBV reactivation with TNF-α inhibitors in RA

Abstract

This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in patients with HBV-related rheumatoid arthritis (RA) undergoing TNF inhibitor (TNFi) therapy. A systematic search of Embase, PubMed/MEDLINE, Scopus, Web of Science, ClinicalTrials.gov and the Cochrane Library was conducted, and pooled HBVr rates were calculated using random-effects models with subgroup analyses based on region, HBV serostatus, glucocorticoid use, antiviral prophylaxis, and TNFi type. Data from 15 studies, including 916 patients, were analyzed, revealing a pooled HBVr rate of 2% (95% CI: 0.01–0.03) with low heterogeneity (I² = 0.79%, p = 0.133). Regional variation was observed, with no HBVr cases in European studies (0.01; 95% CI: −0.01–0.03) and a 2% rate in Asian studies (95% CI: 0.01–0.04). HBsAg-positive patients demonstrated significantly higher HBVr rates (16%; 95% CI: 0.04–0.28) compared with HBsAg-negative patients (4%; 95% CI: −0.01–0.09), corresponding to an odds ratio (OR) of 12.60 (95% CI: 3.73–42.53). Patients receiving antiviral prophylaxis had a 6% HBVr rate compared to 3% in those without prophylaxis, though the difference was not statistically significant (OR: 1.30; p = 0.726). Similarly, glucocorticoid use did not significantly influence HBVr risk (6% vs. 5%; OR: 0.73; p = 0.563). HBVr rates also varied by TNFi type, with 4% for adalimumab, 3% for etanercept, and 2% for infliximab. Overall, TNFi therapy in HBV-related RA is associated with a low but clinically relevant risk of HBVr, with higher rates in HBsAg-positive patients and modest variation by region and drug type, while antiviral prophylaxis and glucocorticoid use appear to have no significant effect on risk.