基于FAERS数据库对恩曲替尼不良事件信号挖掘与分析

Data mining and analysis of adverse event signals of entrectinib based on US FDA adverse event reporting system

目的:基于美国FDA不良事件报告系统(FDA Adverse Event Reporting System,FAERS)数据库挖掘恩曲替尼的不良事件(adverse event,AE)信号,为临床安全用药提供参考。方法:利用OpenVigil 2.1数据平台,收集FAERS数据库中2004年第1季度—2023年第1季度的恩曲替尼相关AE报告,利用比例失衡法中的报告比值比(reporting odds ratio,ROR)法和比例报告比值(proportional reporting ratio,PRR)法进行数据挖掘。结果:共检索到目标药物恩曲替尼相关的AE报告600份,AE报告数呈波动上升趋势;共挖掘到82个AE信号,涉及16种系统器官分类(System Organ Class,SOC),主要为各类神经系统疾病和全身性疾病及给药部位各种反应,其次为肾脏及泌尿系统疾病、心脏系统疾病。报告例次排名靠前的AE信号涉及死亡、头晕、肾功能损坏等首选术语(preferred term,PT),肾功能损害、血肌酐升高、急性肾损伤、心肌炎等PT未被药品说明书收录;信号强度排名靠前的AE信号涉及构音困难、味觉障碍、共济失调等PT,其中构音困难、味觉障碍等大部分PT已被药品说明书收录,肌钙蛋白I升高等PT尚未被药品说明书收录。结论:恩曲替尼导致的AE包括各类神经系统疾病、心脏系统疾病、肾脏及泌尿系统疾病等;临床使用恩曲替尼治疗期间应重点关注患者的各类神经、肾脏和心脏毒性反应。

Objective:To mine adverse event(ADE)signals associated with entrectinib from the FAERS database,providing a reference for safe clinical use.Methods:Utilizing the OpenVigil 2.1 platform,we collected entrectinib-related adverse event reports from the U.S.FDA Adverse Event Reporting System(FAERS)database,spanning from the first quarter of 2004 to the first quarter of 2023.Data mining was performed using the Reporting Odds Ratio(ROR)and Proportional Reporting Ratio(PRR)methods.Results:A total of 600 adverse event reports related to entrectinib were retrieved,showing a fluctuating upward trend.Eighty-two adverse event signals were identified,involving 16 SOC systems,primarily including various nervous system disorders and general disorders and administration site reactions,followed by renal and urinary disorders,and cardiac disorders.The top-ranked ADE signals by report count involved PTs such as death,dizziness,and renal impairment,with PTs like renal impairment,increased blood creatinine,acute kidney injury,and myocarditis not included in the drug's labeling.The top-ranked ADE signals by signal strength involved PTs such as dysarthria,taste disorder,and ataxia,with most of these PTs already included in the drug's labeling,while PTs like elevated troponin I were not included.Conclusion:Entrectinib-related ADEs include various nervous system disorders,cardiac disorders,and renal and urinary disorders.During clinical use of entrectinib,particular attention should be paid to the neurotoxicity,nephrotoxicity,and cardiotoxicity in patients.