Thromboembolic events associated with immune checkpoint inhibitors: A real-world study of data from the food and drug administration adverse event reporting system (FAERS) database
Thromboembolic events associated with immune checkpoint inhibitors: A real-world study of data from the food and drug administration adverse event reporting system (FAERS) database
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与免疫检查点抑制剂相关的血栓栓塞事件：对食品和药物管理局不良事件报告系统 (FAERS) 数据库数据的真实世界研究
DOI：
10.1016/j.intimp.2021.107818
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发表时间：
2021-06-12
影响因子：
5.6
通讯作者：
Zhang, Yuhui
中科院分区：
文献类型：
--
作者：
Li, Hao;Sun, Ximu;Zhang, Yuhui
背景资料：尽管有少数研究报告了接受免疫检查点抑制剂（ICI）治疗的患者发生血栓栓塞事件（TEE），但TEE的详细特征和ICI的促血栓形成作用仍大多未知。方法：检索FAERS数据库中2004年1月至2019年12月的数据。我们调查了TEE的临床特征，并通过使用报告比值比（ROR）将ICI与完整数据库和其他抗癌药物进行比较进行了一致性分析。结果：我们确定了1855例与ICI相关的TEE报告。患者多为男性（59.68%）和65岁以上（47.12%）。报告的TEE的病死率很高（38%）。所有病例的中位至发作时间（TTO）为42（四分位距[IQR] 15-96）天，致死性病例的中位TTO（31 [IQR 13-73]天）显著短于非致死性病例（50 [IQR 20-108]天，p = 0.000002）。与完整数据库相比，ICI显示VTE（ROR 2.81，95% CI 2.69-2.95）和ATE（ROR 1.44，95% CI 1.37-1.52）风险增加。与蛋白激酶抑制剂相比，ICI显示VTE风险增加（ROR 1.23，95% CI 1.17-1.29），但仅抗PD-L1显示脑ATE风险增加（ROR 1.38，95% CI 1.08-1.76）。与化疗相比，ICI显示PE的风险增加（ROR 1.14，95% CI 1.07-1.21）。结论：我们的研究表明ICI倾向于增加VTE和ATE的风险。这些事件的不良临床结局和早期发作应引起临床关注。
Background: Although there have been a few studies reporting thromboembolic events (TEEs) in patients treated with immune checkpoint inhibitors (ICIs), the detailed profile of the TEEs and the prothrombotic effects of ICIs remain mostly unknown. Methods: Data from January 2004 to December 2019 in the FAERS database were retrieved. We investigated the clinical characteristics of the TEEs and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare ICIs with the full database and other anti-cancer agents. Results: We identified 1855 reports of TEEs associated with ICIs. Affected patients tended to be male (59.68%) and older than 65 (47.12%). The case-fatality rate of the reported TEEs was high (38%). The median time to onset (TTO) of all cases was 42 (interquartile range [IQR] 15-96) days and the median TTO of fatal cases (31 [IQR 13-73] days) was significantly shorter than non-fatal cases (50 [IQR 20-108] days, p = 0.000002). ICIs showed increased risks of VTE (ROR 2.81, 95% CI 2.69-2.95) and ATE (ROR 1.44, 95% CI 1.37-1.52) compared with the full database. Compared with protein kinase inhibitors, ICIs showed an increased risk of VTE (ROR 1.23, 95% CI 1.17-1.29), but only anti-PD-L1 showed an increased risk of cerebral ATE (ROR 1.38, 95% CI 1.08-1.76). Compared with chemotherapy, ICIs showed an increased risk of PE (ROR 1.14, 95% CI 1.07-1.21). Conclusions: Our study suggested ICIs tend to increase risks of VTE and ATE. The poor clinical outcome and early onset of these events should attract clinical attention.