Short-Course Tocilizumab Increases Risk Of Hepatitis B Virus Reactivation In Patients With Rheumatoid Arthritis: A Prospective Clinical Observation

AimTo investigate the impact of short-course tocilizumab (TCZ) on hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients.MethodsRA 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.ResultsSixty-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.ConclusionsThis 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.