Short-course tocilizumab increases risk of hepatitis B virus reactivation in patients with rheumatoid arthritis: a prospective clinical observation.

Abstract

To investigate the impact of short-course tocilizumab (TCZ) on hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients. RA patients with moderate to high disease activity, with at least one feature of poor prognosis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were recruited. Three consecutive doses of intravenous TCZ were given combined with csDMARDs. Liver function and HBV infection status were evaluated at baseline, weeks 4, 8 and 12. Sixty-three RA patients who were qualified for statistics were classified as chronic HBV infection (n = 7), resolved HBV infection (n = 41) and non-HBV infection (n = 15). Three patients with chronic HBV infection and without antiviral prophylaxis developed HBV reactivation after 1-3 doses of TCZ. They were asymptomatic of hepatitis B with normal aminotransferases and the HBV-DNA of three patients with HBV reactivation became undetectable after therapeutic antiviral therapy. No HBV reactivation developed in patients with resolved HBV infection. Aminotransferases elevated in 22% of all patients, but became elevated ≥ 2-fold of normal range in only two patients: one was treated with adefovir before TCZ for active hepatitis B and the other had resolved HBV infection, with aminotransferases returning to normal 4 weeks later. Thirty-two patients with resolved HBV infection had positive anti-HBs (≥ 10 IU/L) which is a protective antibody. The anti-HBs titer reduced significantly at week 4 and week 8 after the first dose of TCZ compared to baseline (P < 0.05) and even reduced to negative in six (19%). The anti-HBs did not return to positive in three patients during follow-up of 12-36 weeks. This prospective clinical observation preliminarily indicated three-dose TCZ combined with csDMARDs might increase the risk of HBV reactivation in RA patients with chronic HBV infection, but in this study patients remained asymptomatic and had a benign outcome after antiviral treatment. To identify the exact risk of TCZ on HBV infection and the prognosis of TCZ-related HBV reactivation, further studies with larger sample sizes and fewer confounding factors are needed.