Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：类风湿性关节炎（RA）患者的乙型肝炎核心抗体（HBcAb）血清阳性和乙型肝炎表面抗原（HBsAg）阴性，当使用生物或靶向合成（b/ts）疾病修饰抗风湿药物（DMARDs）治疗时，有乙型肝炎病毒（HBV）重新激活的风险。该研究旨在调查该人群的风险。
方法：从2004年1月到2020年12月，纳入了1068例接受b/tsDMARDs治疗的RA患者和416例HBsAg-/HBcAb+患者。分析与HBV再激活相关的因素。
结果：在2845人年的随访中，416人中的27人（6.5%，9.5每1000人年）患者发展HBV再激活，在5年内HBV再激活的累积率为3.5％，10年为6.1%，17年为24.2%。从开始b/tsDMARDs到HBV再激活的中位间隔为85个月（范围：9-186个月）。HBV再激活的风险因b/tsDMARD类型而异，利妥昔单抗的风险最高（发病率：每1000人年48.3），其次是abatacept（发病率：24.0/1000人年）。在多变量分析中，利妥昔单抗（调整后的风险比[aHR]：15.77，95%置信区间[CI]：4.12-60.32，p=.001），abatacept（AHR：9.30，1.83-47.19，p=.007），阿达木单抗（aHR：3.86，1.05-14.26，p=.04）和阴性基线HBV表面抗体（抗HBs，<10mIU/mL）（aHR：3.89，1.70-8.92，p<.001）是HBV再激活的独立危险因素。
结论：HBsAg-/HBcAb+RA患者在b/tsDMARD治疗期间对HBV再激活易感。那些基线抗HBs阴性的人和那些在某些b/tsDMARD上的人，如利妥昔单抗，abatacept和阿达木单抗，有很高的重新激活风险。风险分层和管理应基于患者的基线抗-HBs滴度和治疗类型。
方法：从2004年1月到2020年12月，纳入了1068例接受b/tsDMARDs治疗的RA患者和416例HBsAg-/HBcAb+患者。分析与HBV再激活相关的因素。
结果：在2845人年的随访中，416人中的27人（6.5%，9.5每1000人年）患者发展HBV再激活，在5年内HBV再激活的累积率为3.5％，10年为6.1%，17年为24.2%。从开始b/tsDMARDs到HBV再激活的中位间隔为85个月（范围：9-186个月）。HBV再激活的风险因b/tsDMARD类型而异，利妥昔单抗的风险最高（发病率：每1000人年48.3），其次是abatacept（发病率：24.0/1000人年）。在多变量分析中，利妥昔单抗（调整后的风险比[aHR]：15.77，95%置信区间[CI]：4.12-60.32，p=.001），abatacept（AHR：9.30，1.83-47.19，p=.007），阿达木单抗（aHR：3.86，1.05-14.26，p=.04）和阴性基线HBV表面抗体（抗HBs，<10mIU/mL）（aHR：3.89，1.70-8.92，p<.001）是HBV再激活的独立危险因素。
结论：HBsAg-/HBcAb+RA患者在b/tsDMARD治疗期间对HBV再激活易感。那些基线抗HBs阴性的人和那些在某些b/tsDMARD上的人，如利妥昔单抗，abatacept和阿达木单抗，有很高的重新激活风险。风险分层和管理应基于患者的基线抗-HBs滴度和治疗类型。
