HBV reactivation in HBsAg−/HBcAb+ rheumatoid arthritis patients receiving biologic/targeted synthetic DMARDs

Abstract

AbstractBackgroundRheumatoid arthritis (RA) patients seropositive for hepatitis B core antibody (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are at risk of hepatitis B virus (HBV) reactivation when treated with biologic or targeted synthetic (b/ts) disease‐modifying antirheumatic drugs (DMARDs). The study aims to investigate the risk in this population.MethodsFrom January 2004 through December 2020, 1068 RA patients undergoing b/tsDMARDs therapy and 416 patients with HBsAg−/HBcAb+ were enrolled. Factors associated with HBV reactivation were analysed.ResultsDuring 2845 person‐years of follow‐up, 27 of 416 (6.5%,9.5 per 1000 person‐years) patients developed HBV reactivation, with a cumulative rate of HBV reactivation of 3.5% at 5 years, 6.1% at 10 years and 24.2% at 17 years. The median interval from beginning b/tsDMARDs to HBV reactivation was 85 months (range: 9–186 months). The risk of HBV reactivation varied by type of b/tsDMARD, with rituximab having the highest risk (incidence rate: 48.3 per 1000 person‐years), followed by abatacept (incidence rate: 24.0 per 1000 person‐years). In multivariate analysis, rituximab (adjusted hazard ratio [aHR]: 15.77, 95% confidence interval [CI]: 4.12–60.32, p = .001), abatacept (aHR: 9.30, 1.83–47.19, p = .007), adalimumab (aHR: 3.86, 1.05–14.26, p = .04) and negative baseline HBV surface antibody (anti‐HBs, <10 mIU/mL) (aHR: 3.89, 1.70–8.92, p < .001) were independent risk factors for HBV reactivation.ConclusionHBsAg−/HBcAb+ RA patients are susceptible to HBV reactivation during b/tsDMARD therapy. Those with negative baseline anti‐HBs and those on certain b/tsDMARDs, such as rituximab, abatacept and adalimumab, have high reactivation risks. Risk stratification and management should be based on the patient's baseline anti‐HBs titre and type of therapy.