免疫检查点抑制剂相关的血栓栓塞事件：来自食品和药物管理局不良事件报告系统（FAERS）数据库的真实世界研究数据。

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.

机构信息

Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Institute of Respiratory Medicine, Beijing 100020, China.

Department of Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100020, China.

出版信息

Int Immunopharmacol. 2021 Sep;98:107818. doi: 10.1016/j.intimp.2021.107818. Epub 2021 Jun 12.

DOI:10.1016/j.intimp.2021.107818

PMID:34130149

Abstract

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.

摘要

背景

尽管已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 的详细情况和 ICI 的促血栓形成作用在很大程度上仍不清楚。

方法

从 FAERS 数据库中检索了 2004 年 1 月至 2019 年 12 月的数据。我们调查了 TEE 的临床特征，并通过报告比值比（ROR）进行了不均衡性分析，以比较 ICI 与整个数据库和其他抗癌药物。

结果

我们确定了 1855 例与 ICI 相关的 TEE 报告。受影响的患者多为男性（59.68%）和 65 岁以上（47.12%）。报告的 TEE 病死率较高（38%）。所有病例的中位发病时间（TTO）为 42（四分位距 [IQR] 15-96）天，致命病例的 TTO（31 [IQR 13-73]天）明显短于非致命病例（50 [IQR 20-108]天，p=0.000002）。与整个数据库相比，ICI 显示出增加的 VTE（ROR 2.81，95%CI 2.69-2.95）和 ATE（ROR 1.44，95%CI 1.37-1.52）风险。与蛋白激酶抑制剂相比，ICI 显示出增加的 VTE 风险（ROR 1.23，95%CI 1.17-1.29），但只有抗 PD-L1 显示出增加的脑 ATE 风险（ROR 1.38，95%CI 1.08-1.76）。与化疗相比，ICI 显示出增加的 PE 风险（ROR 1.14，95%CI 1.07-1.21）。