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

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.