基于美国FDA不良事件报告系统数据库的EGFR抑制剂相关神经系统不良事件风险信号挖掘  

Risk signal mining of adverse events of nervous system related to EGFR inhibitors based on FDA Adverse Events Reporting System database

作　　者：郑园[1] 闫晨[1] 李彬[1] 李正翔[1] 袁恒杰[1] Zheng Yuan;Yan Chen;Li Bin;Li Zhengxiang;Yuan Hengjie(Department of Pharmacy,Tianjin Medical University General Hospital,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院药剂科,天津300052

出　　处：《药物不良反应杂志》2024年第9期524-529,共6页Adverse Drug Reactions Journal

摘　　要：目的挖掘表皮生长因子受体(EGFR)抑制剂相关神经系统不良事件(AE)信号,为临床安全使用该药提供参考。方法利用OpenVigil数据平台收集美国FDA不良事件报告系统(FAERS)数据库中吉非替尼、厄洛替尼、阿法替尼和奥希替尼相关神经系统AE,设定起始时间分别为2004年、2004年、2013年和2015年,截止时间为2023年第2季度。采用国际医学用语词典23.0版的首选术语(PT)对AE进行标准化。从AE报告中提取患者一般情况和神经系统AE等数据。通过报告比值比(ROR)法和比例报告比值比(PRR)法进行AE信号挖掘,同时满足以下条件则视为产生1个AE风险信号:报告数≥3,ROR值的95%置信区间(CI)下限>1,PRR≥2,χ^(2)≥4。结果共收集到吉非替尼相关神经系统AE报告422份,涉及患者297例,PT 42个;检测到风险信号10个,其PT为痴呆症、脑水肿、脱髓鞘、白质脑病、偏瘫、声带麻痹、神经系统症状、脑萎缩、颅内压升高和神经疾病,涉及AE报告64份。厄洛替尼相关神经系统AE报告1755份,涉及患者1477例,PT 69个;检测到风险信号7个,其PT为味觉缺失、感觉过敏、面部疼痛、脱髓鞘、晕动症、声带麻痹和周围神经性麻痹,涉及AE报告142份。阿法替尼相关神经系统AE报告247份,涉及患者212例,PT 32个;检测到风险信号7个,其PT为味觉缺失、脑梗死、脑水肿、癫痫、中枢神经系统损伤、白质脑病和大脑功能障碍,涉及AE报告49份。奥希替尼相关神经系统AE报告652份,涉及患者582例,PT 46个;检测到风险信号3个,其PT为脑梗死、声带麻痹和面瘫,涉及AE报告54份。味觉缺失是阿法替尼说明书中已收录的不良反应,其他AE风险信号均未被说明书收录。结论FAERS数据库中挖掘到的EGFR抑制剂相关神经系统AE风险信号大部分在药品说明书中未收录,临床用药时应注意监测。Objective To mine the adverse events(AE)of nervous system caused by epidermal growth factor receptor(EGFR)inhibitors,and provide reference for the safe use of EGFR inhibitors in clinics.Methods AE of nervous system caused by gefitinib,erlotinib,afatinib and osimertinib were searched from FDA Adverse Drug Event Reporting System(FAERS)database using OpenVigil data platform from 2004,2004,2013,and 2015 to the 2nd quarter of 2023,respectively.The AE was standardized using the preferred term(PT)in the Medical Dictionary for Regulatory Activities 23.0 version.Data such as patient general condition and AE of nervous system was extracted from AE reports and was analyzed descriptively.Reporting odds ratio(ROR)and proportional reporting ratio(PRR)methods were used for detection of AE signal of nervous system.AE that simultaneously met the following conditions was considered as a risk signal:the number of report cases≥3,lower limit of the 95%confidence interval of ROR≥1,PRR≥2,andχ^(2)≥4.Results A total of 422 nervous system AE cases related to gifitinib were collected,involving 297 patients and 42 preferred terms(PT);10 risk signals were detected,including dementia,brain oedema,demyelination,leukoencephalopathy,hemiplegia,vocal cord paralysis,neurological symptom,cerebral atrophy,intracranial pressure increase and neuropathy,with 64 AE cases involved.One thousand seven hundred and fifty-five nervous system AE cases related to erlotinib were collected,involving 1477 patients and 69 PT;7 risk signals were detected,including ageusia,hyperaesthesia,facial pain,demyelination,motion sickness,vocal cord paralysis,peripheral paralysis,with 142 AE cases involved.Two hundred and forty-seven nervous system AE cases related to afatinib were collected,involving 212 patients and 32 PT;7 risk signals were detected,including ageusia,cerebral infarction,brain oedema,epilepsy,central nervous system lesion,leukoencephalopathy,cerebral disorder,with 49 AE cases involved.Six hundred and fifty-two nervous system AE cases related to osim

关 键 词：药物不良反应报告系统 药物相关副作用和不良反应 表皮生长因子受体抑制剂 神经系统相关不良事件 信号挖掘 吉非替尼 厄洛替尼 阿法替尼 奥希替尼 

分 类 号：R969.3[医药卫生—药理学]