Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Can J Cardiol. 2020 Nov;36(11):1739-1746. doi: 10.1016/j.cjca.2020.01.003. Epub 2020 Jan 15.
Tumour necrosis factor inhibitors (TNFis) improve joints outcomes and reduce cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). However, 20%-45% of RA patients are TNFi poor responders and have a significantly higher risk of CV events. In these TNFi nonresponders, the use of second-line biologic agents to improve synovial outcomes is supported by clinical trials and real-world experience. However, it remains unknown what kind of immune-mediated agent has the best CV prevention effect in this high-risk population.
A nationwide RA cohort obtained from Taiwan's National Health Insurance claims database was constructed. RA patients first treated with TNFis who then received either rituximab, tocilizumab, or abatacept were enrolled and followed for 2 years.
A total of 89,973 RA patients were screened and 1,584 patients ultimately included. The incidences of major adverse cardiac events (MACE) at 2 years in the rituximab, tocilizumab, and abatacept groups were 7.17%, 2.75% and 2.38%, respectively. Multivariate adjusted Cox analysis showed that tocilizumab had significantly lower risk than rituximab in myocardial infarction (hazard ratio [HR] 0.12, 95% confidence interval [CI] 0.02-0.56; P = 0.008), and MACE (HR 0.41, 95% CI 0.23-0.72; P = 0.002). In addition, abatacept also had significant lower adjusted risk than rituximab in stroke (HR 0.18, 95% CI 0.05-0.64; P = 0.008), heart failure (HR 0.20, 95% CI 0.05-0.83; P = 0.027), and MACE (HR 0.25, 95% CI 0.11-0.55; P < 0.001) in multivariate analysis.
TNFi-nonresponder patients with RA who received second-line tocilizumab or abatacept had more benefit on CV events prevention compared with those who received rituximab.
肿瘤坏死因子抑制剂（TNFis）可改善类风湿关节炎（RA）患者的关节预后并降低心血管（CV）风险。然而，20%-45%的 RA 患者对 TNFis 反应不佳，CV 事件风险显著增加。在这些 TNFis 无应答者中，临床试验和真实世界经验支持使用二线生物制剂改善滑膜结局。然而，在这种高危人群中，哪种免疫介导的药物具有最佳的 CV 预防效果尚不清楚。
构建了一个来自台湾全民健康保险理赔数据库的全国性 RA 队列。首先接受 TNFis 治疗的 RA 患者，如果随后接受利妥昔单抗、托珠单抗或阿巴西普治疗，则被纳入并随访 2 年。
共筛选出 89973 例 RA 患者，最终纳入 1584 例患者。利妥昔单抗、托珠单抗和阿巴西普组 2 年时主要不良心脏事件（MACE）的发生率分别为 7.17%、2.75%和 2.38%。多变量调整 Cox 分析显示，托珠单抗在心肌梗死（危险比[HR]0.12，95%置信区间[CI]0.02-0.56；P=0.008）和 MACE（HR0.41，95%CI0.23-0.72；P=0.002）方面的风险显著低于利妥昔单抗。此外，阿巴西普在卒中（HR0.18，95%CI0.05-0.64；P=0.008）、心力衰竭（HR0.20，95%CI0.05-0.83；P=0.027）和 MACE（HR0.25，95%CI0.11-0.55；P<0.001）方面的调整风险也显著低于利妥昔单抗。
接受二线托珠单抗或阿巴西普治疗的 RA 患者 TNFis 无应答者在预防 CV 事件方面比接受利妥昔单抗治疗的患者更有获益。
