基于FAERS数据库的决奈达隆不良事件信号挖掘与分析

Signal mining and analysis of adverse events of dronedarone based on FAERS database

目的采用大样本数据挖掘真实世界中决奈达隆相关的不良事件(ADE)信号,为其国内上市后临床安全合理用药提供依据。方法通过Open Vigil 2.1数据平台,收集美国食品药品监督管理局(FDA)不良事件报告系统(FAERS)自药品上市起至2022年12月31日的决奈达隆ADE报告,采用报告比值比法(ROR)和贝叶斯置信传播神经网络(BCPNN)法进行ADE信号挖掘,采用监管活动医学词典(MedDRA)分析药物不良事件发生情况。结果共提取到10930例以决奈达隆为首要怀疑药物的ADE报告,挖掘到170个有效信号,累及18个系统器官分类(SOC)。10930例报告中,男性构成比(42.42%)低于女性(51.27%);年龄主要分布在50岁以上的人群,包括50~69岁(25.35%)和≥70岁(49.59%);累及的SOC主要包括心脏器官疾病、各类检查、呼吸系统、胸及纵隔疾病等;报告数量较多的ADE信号包括房颤、呼吸困难、心力衰竭、血肌酐升高等。挖掘到47个说明书中未记录的新的潜在不良反应,包括房颤、国际标准化比值(INR)升高、甲状腺功能亢进症、急性肾损伤等。结论采用FAERS数据库可以较全面深入地分析决奈达隆上市后出现的不良反应,建议临床用药期间要多关注说明书中未提及的不良反应,有效降低用药风险。

Objective To explore the adverse drug event(ADE)signals related to dronedarone in the real world by using big data,and to provide reference for the rational and safe drug use in clinic after its marketing in China.Methods The Open Vigil 2.1 data platform was used to collect ADE reports from the FDA′s Adverse Event Reporting System(FAERS),the ADE of dronedarone were collected from being approved by FDA to December 31st,2022.ADE signal mining was conducted by reporting odds ratio method(ROR)and Bayesian confidence propagation neural network(BCPNN)method,and the adverse drug events were analyzed by the International Dictionary of Medical Terms(MedDRA).Results A total of 10930 ADE reports with dronedarone as the primary suspect drug were extracted,and 170 valid signals were mined,involving 18 systematic organ classification(SOC).The proportion of male(42.42%)was lower than that of female(51.27%);the age was mainly over 50 years old,including 50~69 years old(25.35%)and≥70 years old(49.59%).The SOC involved mainly included heart organ disease,various examination,respiratory system,chest and mediastinal diseases,etc.High numbers of ADE signals were reported,including atrial fibrillation,dyspnea,heart failure,and elevated creatinine,etc.A total of 47 new potential adverse reactions which were not recorded in the instructions were discovered,including atrial fibrillation,elevated international standardized ratio,hyperthyroidism,acute kidney injury,etc.Conclusion FAERS database can be used to analyze the adverse reactions after marketing of dronedarone in a more comprehensive and in-depth way.It is suggested to pay more attention to the adverse reactions that are not mentioned in the instructions during clinical medication,so as to effectively reduce the risk of medication.