Short-course tocilizumab treatment may induce HBV reactivation in RA
Treatment with three consecutive doses of tocilizumab (TCZ) in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) appears to increase the risk of hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients with chronic HBV infection, although the patients remain asymptomatic and have a benign outcome after antiviral treatment, a study has found.
The study included 63 RA patients with moderate to high disease activity, with at least one feature of poor prognosis and inadequate response to csDMARDs. Of the patients, seven had chronic HBV infection, 41 had resolved HBV infection and 15 had non-HBV infection. Three consecutive doses of intravenous TCZ were given combined with csDMARDs.
Assessments including liver function and HBV infection status were performed at baseline, weeks 4, 8 and 12.
HBV reactivation after one to three doses of TCZ occurred in three patients with chronic HBV infection and without antiviral prophylaxis. These patients were asymptomatic of hepatitis B, having normal aminotransferases. Furthermore, their HBV-DNA became undetectable after therapeutic antiviral therapy. None of the patients with resolved HBV infection developed HBV reactivation.
Aminotransferase elevation was observed in 22 percent of patients, but only two patients exhibited an elevation that was at least twofold of normal range. Of these 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.
Among patients with resolved HBV infection, 32 had positive anti-HBs (≥10 IU/L), which is a protective antibody. The anti-HBs titre from baseline decreased significantly at weeks 4 and 8 after the first dose of TCZ (p<0.05), even dropping to negative in six patients (19 percent). The anti-HBs did not return to positive in three patients during 12 to 36 weeks of follow-up.
Additional studies with larger sample sizes and fewer confounding factors are warranted to identify the exact risk of TCZ on HBV infection and the prognosis of TCZ-related HBV reactivation, researchers said.