Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan.
School of Medicine, Tzuchi University, Hualien, Taiwan.
Liver Int. 2024 Feb;44(2):497-507. doi: 10.1111/liv.15793. Epub 2023 Nov 27.
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.
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.
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.
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.
接受生物制剂或靶向合成（b/ts）疾病修正抗风湿药物（DMARDs）治疗的乙型肝炎核心抗体（HBcAb）阳性和乙型肝炎表面抗原（HBsAg）阴性的类风湿关节炎（RA）患者存在乙型肝炎病毒（HBV）再激活的风险。本研究旨在对此类人群的风险进行调查。
2004 年 1 月至 2020 年 12 月，纳入 1068 例接受 b/tsDMARDs 治疗的 RA 患者和 416 例 HBsAg-/HBcAb+患者。分析了与 HBV 再激活相关的因素。
在 2845 人年的随访期间，416 例患者中有 27 例（6.5%，每 1000 人年 9.5 例）发生 HBV 再激活，HBV 再激活的累积发生率为 5 年时为 3.5%，10 年时为 6.1%，17 年时为 24.2%。从开始 b/tsDMARDs 到 HBV 再激活的中位间隔时间为 85 个月（范围：9-186 个月）。HBV 再激活的风险因 b/tsDMARD 的类型而异，利妥昔单抗的风险最高（发生率：每 1000 人年 48.3 例），其次是阿巴西普（发生率：每 1000 人年 24.0 例）。多变量分析显示，利妥昔单抗（调整后的危险比[aHR]：15.77，95%置信区间[CI]：4.12-60.32，p=0.001）、阿巴西普（aHR：9.30，1.83-47.19，p=0.007）、阿达木单抗（aHR：3.86，1.05-14.26，p=0.04）和基线乙型肝炎表面抗体（抗-HBs，<10 mIU/mL）阴性（aHR：3.89，1.70-8.92，p<0.001）是 HBV 再激活的独立危险因素。
HBsAg-/HBcAb+RA 患者在接受 b/tsDMARD 治疗期间易发生 HBV 再激活。那些基线抗-HBs 阴性的患者以及使用某些 b/tsDMARDs（如利妥昔单抗、阿巴西普和阿达木单抗）的患者，再激活风险较高。应根据患者的基线抗-HBs 滴度和治疗类型进行风险分层和管理。
