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

• Published in: Liver international Vol. 44; no. 2; pp. 497 - 507
• Main Authors: Kuo, Meng Hsuan, Tseng, Chih‐Wei, Ko, Ping‐Hung, Wang, Sz‐Tsan, Lu, Ming‐Chi, Tung, Chien‐Hsueh, Tseng, Kuo‐Chih, Huang, Kuang‐Yung, Lee, Chi‐Hui, Lai, Ning‐Sheng
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2024
• Subjects: abatacept; Antibodies; Arthritis; Autoimmune diseases; bDMARDs; Confidence intervals; HBV reactivation; Hepatitis; Hepatitis B; Hepatitis B surface antigen; hepatitis flare‐up; JAK inhibitor; Monoclonal antibodies; Multivariate analysis; resolved HBV; Rheumatoid arthritis; Risk factors; Rituximab; Therapy; TNF‐alpha inhibitor; tsDMARDs; tsDMARDs; bDMARDs; HBV reactivation; abatacept; JAK inhibitor; hepatitis flare-up; resolved HBV; rheumatoid arthritis; rituximab; TNF-alpha inhibitor
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/liv.15793

Background Rheumatoid 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. Methods From 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. Results During 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. Conclusion HBsAg−/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.