Long-term safety of rituximab in rheumatic patients with previously resolved hepatitis B virus infection

Abstract

Conflicting results can be found in the literature on the frequency of hepatitis B virus (HBV) reactivation (HBVr) on rituximab (RTX) in rheumatic patients with previously resolved HBV (prHBV) infection. Here, we report the frequency of HBVr in a large historical cohort of caucasian rheumatic patients with prHBV receiving RTX. Registry data of rheumatic patients treated with RTX were retrospectively analysed. Demographic and clinical characteristics including evaluation of anti-HCV and HBV markers, annual HBV-DNA determination and aminotransferase levels assessed every three months, were recorded. Kaplan-Meier estimate was used to compare the risk of being still under therapy at different time points in patients with or without prHBV infection. Cox regression analysis was used to determine the association between recorded variables and treatment discontinuation. A total of 311 patients treated with RTX, 44 (14.1%) with and 267 (85.9%) without prHBV were analysed. No significant difference between the two groups regarding demographic and clinical characteristics was observed. During RTX treatment, detectable HBV-DNA and reappearance of HBsAg in patients with prHBV (seroreversion) were never observed. Kaplan-Meier functions were similar in patients with or without prHBV infection which was not associated with RTX discontinuation neither at univariate nor at multivariate analysis. These data are in favor of the concept that patients with rheumatologic diseases have a very low risk of reactivation of the HBV infection under RTX treatment. However, future prospective studies, including a larger number of patients, are still necessary to draw definitive conclusions.

Systematic literature review informing the 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases

“…On the other hand, in an Italian study, seroconversion and positive HBV-DNA levels were recorded in 0% and 3%, respectively, in 33 patients with RA treated with rituximab 151. In another study, HBV reactivation was not seen in 44 RA, anti-HBcore-positive patients treated with rituximab 152. A recent study, examining 489 patients with resolved HBV, also showed that treatment with rituximab or abatacept were independent risk factors for HBsAg conversion (HR 87.76, 95% CI 11.50 to 669.73, p<0.001; HR 60.57, 95% CI 6.99 to 525.15, respectively) in patients with resolved HBV 153.…”

“… 151 In another study, HBV reactivation was not seen in 44 RA, anti-HBcore-positive patients treated with rituximab. 152 A recent study, examining 489 patients with resolved HBV, also showed that treatment with rituximab or abatacept were independent risk factors for HBsAg conversion (HR 87.76, 95% CI 11.50 to 669.73, p<0.001; HR 60.57, 95% CI 6.99 to 525.15, respectively) in patients with resolved HBV. 153 Data on tsDMARDs are limited.…”