基于美国FAERS数据库的阿可替尼ADE信号挖掘与分析

Mining and analysis of acalabrutinib-induced ADE risk signals based on FDA adverse event reporting system

目的挖掘和分析阿可替尼的药物不良事件(ADE)信号,为其临床安全应用提供参考。方法通过OpenVigil 2.1平台提取美国FDA不良事件报告系统数据库中2017年11月1日至2023年3月31日与阿可替尼相关的ADE报告,采用报告比值比法与英国药品和健康产品管理局综合标准法对ADE信号进行检测。结果提取到以阿可替尼为首要怀疑药物的报告7869份,从中检测到142个ADE阳性信号,涉及20个系统器官分类,基本与其药品说明书记载的ADE一致,主要涉及全身性疾病及给药部位各种反应、各类检查、血液及淋巴系统疾病、各类神经系统疾病和心脏器官疾病等。此外,还发现了一些未在其药品说明书中提及的新的潜在ADE信号,包括心源性猝死、肺毒性、肿瘤溶解综合征、胸腔积液、消化不良、胃食管反流病、骨痛、血压降低、血钠异常等。结论在应用阿可替尼时,除了需要关注其说明书已记载的ADE外,还应评估其包括心源性猝死、肺毒性等可能导致死亡的严重ADE风险,尽可能避免或减少ADE的发生。

OBJECTIVE To provide reference for the clinically safe application of acalabrutinib by mining and analyzing the risk signals of adverse drug events(ADE).METHODS The acalabrutinib-induced ADE reports were extracted from the U.S.FDA adverse event reporting system using the OpenVigil 2.1 platform from November 1,2017 to March 31,2023.The reporting odds ratio(ROR)method and composite criteria method from the Medicines and Healthcare Products Regulatory Agency(MHRA)were used for detection of ADE signals.RESULTS There were 7869 ADE reports of acalabrutinib as the primary suspect drug and 142 ADE positive signals were detected from them,involving 20 system organ classes,which was generally consistent with the ADE recorded in the drug instruction of acalabrutinib,mainly involving general disorders and administration site conditions,various inspection,blood and lymphatic system disorders,various neurological disorders and cardiac disorders.In addition,this study identified several new potential ADE signals that were not mentioned in the drug instruction,including sudden cardiac death,pulmonary toxicity,tumor lysis syndrome,pleural effusion,dyspepsia,gastroesophageal reflux disease,bone pain,decreased blood pressure,and abnormal blood sodium,etc.CONCLUSIONS When using acalabrutinib,in addition to paying attention to the ADE recorded in its instructions,the risk of serious ADE that may lead to death,such as sudden cardiac death and pulmonary toxicity,should also be evaluated to avoid or reduce the occurrence of ADE as much as possible.