基于美国FDA不良事件报告系统数据库的司来帕格不良事件信号挖掘

Mining and analysis of adverse event signals of selexipag based on FDA adverse event reporting system database

目的 挖掘分析司来帕格上市后潜在的药物不良事件(ADE)信号,为临床合理使用提供参考。方法 提取美国FDA不良事件报告系统(FAERS)数据库中司来帕格自2015年12月21日上市至2023年11月9日接收的ADE报告,并对数据进行处理去重和标准化。采用报告比值比(ROR)法和贝叶斯置信度递进神经网络(BCPNN)法进行ADE信号挖掘。结果 共检索到以司来帕格为首要怀疑药物的ADE报告共10 007例。经ROR法和BCPNN法进行检测筛选,获得325个首选术语(PT)信号,累及19个系统器官分类,ADE报告频次以全身性疾病及给药部位各种反应最多(17.24%),其次是胃肠系统疾病(13.62%)、呼吸系统、胸及纵隔疾病(10.86%)、神经系统疾病(10.17%)、肌肉骨骼及结缔组织疾病(9.30%)、各类检查(6.61%)、感染及侵染类疾病(5.23%)等。与药品说明书进行比对发现,司来帕格药品说明书未记载的PT有301种,如呼吸困难、肺动脉压力升高、疲劳、心力衰竭等,临床需给予高度关注。结论 对司来帕格真实世界的ADE进行挖掘,提示临床需慎重评估司来帕格ADE危险因素,加强用药监护,保障患者用药安全。

Objective To mine and analyse the potential adverse event(ADE)risk signals of selexipag post-marketing to provide a reference for its rational clinical application.Methods The FDA adverse event reporting system database of ADEs reported for selexipag from marketing(December 2015)to November 2023 was extracted to conduct data cleaning de-duplication and standardization.Signal mining was performed using the reported ratio(ROR)and Bayesian confidence progressive neural network(BCPNN)methods.Results A total of 10007 ADEs were reported in the database with selexipag as the primary suspect.Mining by ROR and BCPNN methods resulted in 325 potential positive PTs,involving 19 SOCs,among which the ADEs reports associated with general disorders and administration site conditions diseases were the most(17.24%),followed by gastrointestinal system diseases(13.62%),respiratory system,chest and mediastinal diseases(10.86%),nervous system disease(10.17%),musculoskeletal and connective tissue diseases(9.30%),various abnormal examination indicators(6.61%),infectious diseases(5.23%)Compared with the drug instructions,it was found that 301 kinds of PT were not recorded in the drug instructions,such as dyspnea,elevated pulmonary artery pressure,fatigue,heart failure and so on,which require high clinical attention.Conclusion Mining the real-world adverse events of selexipag suggests that clinical caution should be given in evaluating its ADE risk factors and strengthening the medication monitoring to ensure patient medication safety.