基于FAERS的恩曲替尼药品不良事件信号挖掘

Signal Mining of Entrectinib-Related Adverse Drug Events Based on FAERS Database

目的为恩曲替尼的临床安全使用提供参考。方法检索美国食品和药物管理局不良事件报告系统(FAERS)中2019年6月至2023年3月的恩曲替尼相关药品不良事件(ADE)报告,采用报告比值比(ROR)法和比例报告比(PRR)法挖掘ADE信号,采用MedDRA 25.0中的首选语(PT)、系统器官分类(SOC)对相关药品不良反应(ADR)名称进行规范性表达。结果共检索到恩曲替尼相关ADE报告600份,涉及患者600例,男女性别比为1∶1.27,美国报告例数最多(49.17%)。共挖掘到80个ADE信号,累及15个SOC,主要包括各类神经系统疾病(13个)、各类检查(11个)、心脏器官疾病(8个)等。ADE报告数排名前3的PT分别为死亡(61例)、头晕(60例)、肾功能损害(38例),ADE信号强度排名前3的PT分别为呼吸困难(PRR=254.501)、淋巴管瘤(PRR=125.753)、肌钙蛋白I升高(PRR=90.203)。共发现药品说明书中未提及的ADR 27个,主要为死亡(61例)、肾功能损害(38例)、心力衰竭(26例)。结论挖掘到的恩曲替尼ADR与药品说明书基本一致,临床用药时除关注药品说明书中已提及的ADR外,还需密切关注患者的心功能、肾功能等,以便及时发现并处理新的ADR,保障用药安全。

Objective To provide a reference for the safe clinical use of entrectinib.Methods The entrectinib-related adverse drug event(ADE)reports in the Food and Drug Administration Adverse Event Reporting System(FAERS)system were searched,and the ADE signals were mined by the reporting odds ratio(ROR)method and proportional reporting ratio(PRR)method.The preferred term(PT)and system organ classifications(SOC)in MedDRA 25.0 were used to standrdize the expression of aduerse drug reactions(ADRs).Results A total of 600 entrectinib-related ADE reports were searched,involving 600 patients with a male-to-female ratio of 1∶1.27,with the highest number reported in the United States(49.17%).Eighty ADE signals were excavated,involving fifteen SOC,mainly including various nervous system diseases(thirteen signals),various examinations(eleven signals),heart organ diseases(eight signals),etc.The top three PT in terms of the number of ADE reports were death(61 cases),dizziness(60 cases),and renal dysfunction(38 cases).The top three PT in terms of the intensity of ADE signals were dyspnea(PRR=254.501),lymphangioma(PRR=125.753),and elevated troponin I(PRR=90.203).A total of 27 ADRs were found that were not listed in the package insert,mainly including deaths(61 cases),renal dysfunction(38 cases),and heart failure(26 cases).Conclusion The entrectinib-related ADRs excavated are basically consistent with those listed in the package insert.In addition to the ADRs listed in the package insert,it is also necessary to pay close attention to the cardiac function and kidney function of patients during the clinical use of drugs,in order to timely detect and deal with new ADRs and ensure the medication safety of patients.