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.
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。