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  

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

作　　者：孙熙木 周涵 李雁铭 郭鹏 聂晓璐[2,3] SUN Ximu;ZHOU Han;LI Yanming;GUO Peng;NIE Xiaolu(Department of Pharmacy,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing 100045,China;Center for Clinical Epidemiology&Evidencebased Medicine,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing 100045,China;Hainan Institute of Real World Data,Qionghai Hainan 571437,China)

机构地区：[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

出　　处：《中国药物警戒》2025年第1期23-28,共6页Chinese Journal of Pharmacovigilance

基　　金：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(QML20231204);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)。

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2050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(IC_(025))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(IC_(025)=0.07)和阿维鲁单抗(IC_(025)=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。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 2050 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(IC_(025))while those of immune thrombocytopenia were moderate except for cemiplimab(IC_(025)=0.07)and avelumab(IC_(025)=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.

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 

分 类 号：R994.1[医药卫生—毒理学] R978[医药卫生—药学]