基于美国FDA不良事件报告系统数据库的依瑞奈尤单抗风险信号挖掘

Signal mining of adverse events related to erenumab based on the US FDA Adverse Event Reporting System database

目的挖掘并分析依瑞奈尤单抗主要不良事件信号,为该药临床安全应用提供参考。方法从美国FDA不良事件报告系统数据库提取2004年至第2023年第1季度关于依瑞奈尤单抗不良事件(AE)报告,分别对全数据和2018年以后数据进行分析。采用国际医学用语词典(MedDRA)23.0版的首选术语(PT)和系统器官分类(SOC)对AE进行分类统计。采用报告比值比(ROR)法和贝叶斯置信传播神经网络(BCPNN)法进行AE风险信号的挖掘。结果共收集到以依瑞奈尤单抗为首要怀疑药物的AE报告38348份,涉及PT为2629个。基于全数据和2018年以后数据,挖掘到依瑞奈尤单抗AE风险信号分别为99和115个,均涉及19个SOC,其中上报例数最多的AE为注射部位反应和便秘,与说明书记载一致。信号强度居前30位的PT中,13个未被说明书收录,包括松果体囊肿、体位性心动过速综合征、组蛋白抗体阳性、痉挛性眼球运动、注射恐惧、脑震荡后综合征、雷诺现象、精神性癫痫发作、冠状动脉夹层、过早绝经、脆发症、胶原病、睑痉挛。结论临床应用依瑞奈尤单抗时,除说明书中记载的不良反应外,本研究中挖掘出的不良事件也应给予关注。

Objective To mine and analyze the signals of the adverse event(AE)of erenumab and provide reference for the safe application of the drug.Methods The reports of AE from 2004 to the first quarter of 2023 were extracted from the US FDA Adverse Event Reporting System database,and the full data and data after 2018 were analyzed respectively.AEs were classified according to preferred term(PT)and the system organ class(SOC)of Medical Dictionary for Regulatory Activities(MedDRA)23.0version for statistical analysis.The reported odds ratio(ROR)method and Bayesian confidence progressive neural network(BCPNN)method were used to mine the AE risk signals.Results A total of 38348 AE reports with erenumab as the primary suspect drug were collected,involving 2629 PTs.The number of risk signals screened by the ROR and BCPNN methods from the full data and data after 2018 was 99 and 115,respectively,involving 19 SOCs.Among them,the most frequently reported AEs were injection site reactions and constipation,which were consistent with the label.Among the top 30 PTs,13 were not recorded in the label,including pineal cyst,postural tachycardia,positive histone antibody,spastic eye movements,fear of injection,post‑concussion syndrome,Raynaud effect,psychogenic seizures,coronary artery dissection,premature menopause,trichorrhexis,collagen disease,and blepharospasm.Conclusion In clinical application of erenumab,in addition to the adverse reactions recorded in the label,attention should also be paid to the adverse events mined in this study.