基于美国FAERS数据库的KRAS G12C抑制剂不良事件不相称测定分析  

Disproportionality of Adverse Events to KRAS G12C Inhibitors Based on the FAERS Database

作　　者：朱志朋 吕强 叶小飞[4] 郭晓晶 ZHU Zhipeng;LYU Qiang;YE Xiaofei;GUO Xiaojing(Department of Bone Oncology,the Second Affiliated Hospital of Naval Medical University,Shanghai 200003,China;College of Basic Medical Sciences,Naval Medical University,Shanghai 200433,China;Department of Thoracic Surgery,the Second Affiliated Hospital of Naval Medical University,Shanghai 200003,China;Department of Military Health Statistics,Faculty of Medical Services,Naval Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学第二附属医院骨肿瘤科,上海200003 [2]海军军医大学基础医学院,上海200433 [3]海军军医大学第二附属医院胸外科,上海200003 [4]海军军医大学卫生勤务学系军队卫生统计学教研室,上海200433

出　　处：《中国药物警戒》2025年第3期297-304,共8页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(82073671、81703296);上海市卫生健康委员会科研项目(202340038)。

摘　　要：目的分析KRAS G12C抑制剂索托拉西布与阿达格拉西布的不良事件信号,为临床安全用药提供参考。方法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,提取2021年第3季度至2024年第2季度数据,采用报告比值比法(ROR)、英国药品和保健产品管理局(MHRA)的综合标准法、信息比法(IC)和经验贝叶斯几何平均法(EBGM)进行信号挖掘。结果索托拉西布主要与肝胆系统疾病不良事件相关(n=329,IC_(025)=3.06),信号最强的不良事件是肝脏毒性(n=76,IC_(025)=5.14);阿达格拉西布主要与各种手术及医疗操作(n=102,IC_(025)=1.65)及代谢及营养类疾病(n=76,IC_(025)=0.97)不良事件相关,信号最强的不良事件是心电图QT间期延长(n=11,IC_(025)=2.87)。罕见反应包括索托拉西布的肺栓塞和阿达格拉西布的癫痫持续状态。性别差异和累积剂量显著影响不良事件发生。结论临床应用中需加强索托拉西布和阿达格拉西布不良反应监测,特别是对罕见和严重不良反应,以提高用药安全性。Objective To analyze the adverse event signals of KRAS G12C inhibitors,sotorasib and adagrasib,so as to provide a reference for clinical safety.Methods Data on adverse events reported from Q32021 to Q22024 was retrieved from the US Food and Drug Administration Adverse Event Reporting System(FAERS)database before related signals were mined using the reporting odds ratio(ROR),the comprehensive standard method of the Medicines and Healthcare Products Regulatory Agency(MHRA),the Information Component(IC)method,and the Empirical Bayes Geometric Mean(EBGM)method.Results Sotorasib was primarily associated with adverse reactions related to hepatobiliary disorders(n=329,IC_(025)=3.06),with the strongest signal for hepatotoxicity(n=76,IC_(025)=5.14)while adagrasib was associated with surgical and medical procedures(n=102,IC_(025)=1.65)and metabolism and nutrition disorders(n=76,IC_(025)=0.97),with the strongest signal for electrocardiogram QT prolonged(n=11,IC_(025)=2.87).Rare reactions included pulmonary embolism for sotorasib and status epilepticus for adagrasib.Gender and cumulative doses made a big difference to the incidence of adverse reactions.Conclusion In clinical application,it is necessary to strengthen the monitoring of adverse reactions of sotorasib and adaglasib,especially rare and serious adverse reactions,to improve drug safety.

关 键 词：KRAS G12C抑制剂 索托拉西布 阿达格拉西布 不良事件 肝脏毒性 心电图QT间期延长 神经毒性 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] R979.1[医药卫生—药学]