The Risk of Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Receiving Tocilizumab: A Systematic Review and Meta-Analysis

Abstract

Background: Tocilizumab has demonstrated optimal efficacy and safety in patients with rheumatoid arthritis (RA) from clinical trials. However, the risk of hepatitis B virus reactivation (HBVr) in these patients remains uncertain because patients with underlying HBV have been excluded in phase III studies. Methods: Systematical reviews were conducted on PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to 21 February 2023. Random-effects meta-analysis was performed to calculate the pooled incidence of HBV reactivation. Results: We included 0 clinical trials and 11 observational studies with a total of 25 HBsAg+ and 322 HBsAg−/anti-HBc+ RA patients. Among the HBsAg+ patients without antiviral prophylaxis, the pooled rate was 69.4% (95% CI, 32.9–91.3), with a median time of 4 months (range, 1–8 months) from tocilizumab initiated. Half of these patients with HBVr experienced hepatitis flare-up but no deaths. HBVr was eliminated with prophylaxis in this population. Among HBsAg−/anti-HBc+ patients, the pooled incidence of reactivation was 3.3% (95% CI, 1.6–6.7), with a median time of 10 months (range, 2–43 months) from tocilizumab initiated. HBVr was not associated with hepatitis flare-up and death. HBsAg−/anti-HBc+ patients without anti-HBs antibodies had a significantly higher risk of HBVr (Odds ratio, 12.20; 95% CI, 1.16–128.06). Conclusions: This systematic review indicated that the risk of HBVr in RA patients with anti-HBs−, HBsAg+, or HBsAg−/anti-HBc+ cannot be ignored but may be avoided. Clinicians should consider implementing appropriate antiviral prophylaxis and monitoring policies for RA patients to avoid unnecessary hepatic side effects from tocilizumab treatment.