中国药物警戒 ›› 2025, Vol. 22 ›› Issue (1): 23-28.
DOI: 10.19803/j.1672-8629.20240875

• 药源性血小板减少研究专栏 • 上一篇    下一篇

基于美国FAERS数据库的免疫检查点抑制剂相关血小板减少症信号挖掘与分析

孙熙木1, 周涵1, 李雁铭1, 郭鹏1#, 聂晓璐2,3,*   

  1. 1国家儿童医学中心,首都医科大学附属北京儿童医院药学部, 北京 100045;
    2国家儿童医学中心,首都医科大学附属北京儿童医院临床流行病与循证医学中心,北京 100045;
    3海南省真实世界数据研究院,海南 琼海 571437
  • 收稿日期:2024-11-14 出版日期:2025-01-15 发布日期:2025-01-22
  • 通讯作者: *聂晓璐,女,博士,副研究员,药物流行病学与循证医学。E-mail：niexiaolu@ccmu.edu.cn#为共同通信作者。
  • 作者简介:孙熙木,女,硕士,药师,临床药学。
  • 基金资助:
    国家自然科学基金资助项目（82204149、72404198）; 北京市医院管理中心“青苗”计划专项经费资助（QML2023 1204）; 国家药监局药品监管科学体系建设重点项目（RS2024G001）; 海南博鳌乐城国际医疗旅游先行区真实世界研究专项计划项目（HNLC2022RWS015）

Signal Mining and Analysis of ICIs-Associated Thrombocytopenia Adverse Events Based on FAERS Database

SUN Ximu1, ZHOU Han1, LI Yanming1, GUO Peng1#, NIE Xiaolu2,3,*   

  1. 1Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China;
    2Center for Clinical Epidemiology & Evidence-based Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China;
    3Hainan Institute of Real World Data, Qionghai Hainan 571437, China
  • Received:2024-11-14 Online:2025-01-15 Published:2025-01-22

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摘要： 目的 基于美国食品药品监督管理局不良事件报告系统（FAERS）数据库对免疫检查点抑制剂（ICIs）相关血小板减少症不良事件（AE）信号挖掘,以期为临床安全用药提供参考。方法 提取美国FAERS数据库2011年第1季度至2024年第2季度ICIs相关血小板减少症的AE报告,采用报告比值比法（ROR）和信息成分法（IC）进行信号挖掘。结果 共获得ICIs为首要怀疑药物（PS）所致血小板减少症的AE报告共2 050份,多见于男性（52.29%）和老年（44.73%）人群。报告最多的国家为日本（19.95%）,适应证多分布于肺部（33.41%）和皮肤（13.41%）。除细胞毒性T淋巴细胞相关抗原4（CTLA-4）抑制剂外,程序性死亡受体1（PD-1）抑制剂和程序性死亡受体配体1（PD-L1）抑制剂在血小板减少症和免疫性血小板减少症上均检测到阳性信号。血小板减少症阳性信号按照信息成分（IC025）分类为弱强度信号。免疫性血小板减少症阳性信号除西米普利单抗（IC025=0.07）和阿维鲁单抗（IC025=0.57）外均为中等强度信号,尤其PD-L1抑制剂和CTLA-4抑制剂联合方案ROR值最高 [ROR=26.15(13.04~52.45)]。结论 医务人员应警惕ICIs可能导致的血小板减少症不良事件并及时予以预防或治疗方案,以提高ICIs的临床应用安全性。

关键词: 免疫检查点抑制剂, 血小板减少症, 药品上市后安全监测, 信号挖掘, 美国食品药品监督管理局不良事件报告系统

Abstract: Objective To explore the immune checkpoint inhibitors (ICIs)-associated thrombocytopenia adverse events (AE) based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database in order to provide a reference for the safe use of ICIs in clinic. Methods AE reports on ICIs-related thrombocytopenia collected from the first quarter of 2011 to the second quarter of 2024 in the FAERS database were retrieved. Signals were mined using the reporting odds ratio (ROR) and information component (IC) methods. Results A total of 2 050 AE reports with ICIs as the primary suspected drug (PS) associated with thrombocytopenia were obtained, involving a higher percentage of males (52.29%) and elders (44.73%). The country that submitted the largest number of reports was Japan (19.95%). Indications were prevalent in the lungs (33.41%) and skin (13.41%). Except for cytotoxic T lymphocyte associated antigen-4 (CTLA-4) inhibitors, positive signals related to programmed death receptor 1 (PD-1) inhibitors and programmed death receptor ligand 1 (PD-L1) inhibitors were detected in both thrombocytopenia and immune thrombocytopenia. The positive signals of thrombocytopenia were classified as weak ones according to the information component (IC025) while those of immune thrombocytopenia were moderate except for cemiplimab (IC025=0.07) and avelumab (IC025=0.57), and the combination of PD-L1 inhibitor and CTLA-4 inhibitor had the highest ROR value [RR=26.15 (13.04~52.45)]. Conclusion Clinicians should be alert to the potential AE of thrombocytopenia caused by ICIs and promptly implement prevention or treatment strategies to improve the safety of ICIs in clinical application.

Key words: Immune Checkpoint Inhibitors, Thrombocytopenia, Post-Marketing Pharmacovigilance, Signal Mining, FAERS

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