戈沙妥珠单抗的药物不良事件信号挖掘与分析

Signal mining and analysis of adverse events of sacituzumab govitecan

目的挖掘戈沙妥珠单抗的药物不良事件(ADE)信号,为其临床安全用药提供参考。方法收集美国FDA不良事件报告系统(FAERS)2020年4月1日至2024年4月30日上报的戈沙妥珠单抗ADE数据。采用报告比值比法、英国药品和保健品管理局综合标准法、贝叶斯置信度递进神经网络法进行数据挖掘。利用《国际医学用语词典》27.0版ADE术语集中的系统器官分类(SOC)、首选术语(PT)进行分类统计。结果共得到戈沙妥珠单抗ADE报告753份,包括46个ADE信号,涉及12个SOC、13个说明书中未记载的新的可疑的ADE信号。发生频次排名前5位的PT分别为疾病进展、死亡、腹泻、超说明书使用、产品给予时间表不当。信号强度排名前5位的PT分别为发热性骨髓再生障碍、中性粒细胞减少性结肠炎、疾病进展、肺脓毒症、一般身体状况异常。药品说明书未记录的新的可疑的ADE包括中性粒细胞减少性脓毒症、肝细胞溶解、脑膜炎、发育不全等。结论临床使用戈沙妥珠单抗时,应特别关注发热性中性粒细胞减少症、发热性骨髓再生障碍、体重波动、结肠炎等报告例数多且信号强度高的ADE;还应警惕中性粒细胞减少性脓毒症、肝细胞溶解、脑膜炎、发育不全等新的可疑的ADE,以保障患者用药安全。

OBJECTIVE To mine the adverse drug event(ADE)signals of sacituzumab govitecan and provide a reference for its clinical safety application.METHODS The data of sacituzumab govitecan-related ADE reports were collected from the FDA Adverse Event Reporting System(FAERS)database from April 1,2020 to April 30,2024.The reporting odds ratio(ROR)method,the United Kingdom Medicines and Healthcare Products Regulatory Agency comprehensive standard method(MHRA)and Bayesian confidence propagation neural network(BCPNN)method were used for data mining.Systematic organ classification(SOC)and preferred term(PT)in the ADE terminology set of version 27.0 of the Medical Dictionary for Regulatory Activities(MedDRA)were used for data classification and statistics.RESULTS A total of 753 ADE reports were obtained for sacituzumab govitecan,including 46 ADE signals,involving 12 SOCs,and 13 new suspicious ADE signals not recorded in the instructions.Top 5 PTs in terms of occurrence frequency were disease progression,death,diarrhea,off label use and inappropriate schedule of product administration.Top 5 PTs in terms of signal strength were febrile bone marrow aplasia,neutropenic colitis,disease progression,pulmonary sepsis,general physical condition abnormal.New ADE not recorded in the drug instructions included neutropenic sepsis,hepatic cytolysis,meningitis,aplasia,etc.CONCLUSIONS When using sacituzumab govitecan in clinical practice,special attention should be paid to ADE with highly reported cases and strong signal intensity,such as febrile neutropenia,febrile bone marrow aplasia,weight fluctuations,colitis.We should also be alert to new suspected ADE such as neutropenic sepsis,hepatic cytolysis,meningitis,and aplasia to ensure patient medication safety.