University of Alabama, Birmingham.
Arthritis Care Res (Hoboken). 2019 Aug;71(8):1004-1018. doi: 10.1002/acr.23737.
Multiple studies have shown seemingly unfavorable changes in lipid profiles associated with interleukin-6 receptor (IL-6R) antagonists and some other therapies for rheumatoid arthritis. The aim of this study was to assess the real-world cardiovascular disease (CVD) risk associated with tocilizumab, the first anti-IL-6R medication approved for the treatment of RA.
We conducted a cohort study using 2006-2015 Medicare and MarketScan claims for patients with RA in whom treatment with biologic disease-modifying antirheumatic drugs was initiated after January 1, 2010. The primary outcome was a composite of myocardial infarction, stroke, and fatal CVD, assessed using a validated method. The influence of potential confounding due to RA disease activity was assessed in a subgroup analysis (~5-10% of biologic therapy initiations) using the multi-biomarker disease activity (MBDA) score.
A total of 88,463 patients with RA were included. The crude incidence rate (IR) per 1,000 patient-years for composite CVD events among Medicare patients ranged from 11.8 (95% confidence interval [95% CI] 9.7-14.4) for etanercept users to 17.3 (95% CI 15.2-19.7) for infliximab users. The crude IR for pooled users of a tumor necrosis factor inhibitor was 15.0 (95% CI 13.9-16.3). Compared to tocilizumab, the corresponding adjusted hazard ratios (HRs) were 1.01 (95% CI 0.79-1.28) for abatacept, 1.16 (95% CI 0.89-1.53) for rituximab, 1.10 (95% CI 0.80-1.51) for etanercept, 1.33 (95% CI 0.99-1.80) for adalimumab, and 1.61 (95% CI 1.22-2.12) for infliximab. There were no statistically significant differences in the risk of CVD between tocilizumab and any other biologic when MarketScan data were used. Results were robust in numerous subgroup analyses and after external adjustment to control for RA disease activity in the subgroup of patients with linked MBDA test results (n = 4,156).
Tocilizumab was associated with a CVD risk comparable to that for etanercept as well as a number of other biologics used for the treatment of RA.
多项研究表明，白细胞介素 6 受体（IL-6R）拮抗剂和其他一些类风湿关节炎治疗药物与血脂谱的一些看似不利的变化有关。本研究旨在评估托珠单抗（第一种用于治疗 RA 的抗 IL-6R 药物）与心血管疾病（CVD）风险的真实关联。
我们使用 2006 年至 2015 年 Medicare 和 MarketScan 中接受生物疾病修饰抗风湿药物治疗的 RA 患者的索赔数据进行了队列研究，这些患者在 2010 年 1 月 1 日后开始接受治疗。主要结局是使用经过验证的方法评估心肌梗死、中风和致命性 CVD 的复合结局。在亚组分析（生物治疗开始后约 5-10%）中，使用多生物标志物疾病活动（MBDA）评分评估 RA 疾病活动引起的潜在混杂因素的影响。
共纳入 88463 例 RA 患者。 Medicare 患者中复合 CVD 事件的粗发生率（IR）为每 1000 患者年 11.8（95%置信区间 [95%CI]9.7-14.4），依那西普使用者为 17.3（95%CI 15.2-19.7），肿瘤坏死因子抑制剂的总使用者为 15.0（95%CI 13.9-16.3）。与托珠单抗相比，阿巴西普的相应校正风险比（HR）为 1.01（95%CI 0.79-1.28），利妥昔单抗为 1.16（95%CI 0.89-1.53），依那西普为 1.10（95%CI 0.80-1.51），阿达木单抗为 1.33（95%CI 0.99-1.80），英夫利昔单抗为 1.61（95%CI 1.22-2.12）。当使用 MarketScan 数据时，托珠单抗与任何其他生物制剂在 CVD 风险方面没有统计学上的显著差异。在大量亚组分析中以及在与 MBDA 检测结果相关的患者亚组（n=4156）中外部调整以控制 RA 疾病活动后，结果仍然稳健。
托珠单抗与依那西普以及其他一些用于治疗 RA 的生物制剂的 CVD 风险相当。
