基于FAERS数据库的MET-TKIs上市后相关药品不良反应信号挖掘  

Signal mining of adverse drug reaction related to MET-TKIs after marketing based on FAERS database

作　　者：王美飒 韩秋爽 高靓[2] 蒋媛[2] 陈喆 WANG Meisa;HAN Qiushuang;GAO Liang;JIANG Yuan;CHEN Zhe(National Cancer Center/National Clinical Research Center for Cancer/Department of Pharmacy Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Department of Pharmacy,Tianjin Union Medical Center(The First Affiliated Hospital of Nankai University),Tianjin 300121,China;Tianjin Adverse Reaction Monitoring Center for Drugs Medical Devices and Cosmetics,Tianjin 300191,China)

机构地区：[1]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院药剂科,北京100021 [2]天津市人民医院(南开大学第一附属医院)药学部,天津300121 [3]天津市药品医疗器械化妆品不良反应监测中心,天津300191

出　　处：《药学前沿》2025年第2期300-310,共11页China Pharmacist

基　　金：国家卫生健康委医药卫生科技发展研究中心面上课题项目(WKZX2023CX210003)。

摘　　要：目的基于美国食品药品监督管理局不良事件报告系统(FAERS)数据库,挖掘4种间质-上皮转换因子酪氨酸激酶抑制剂(MET-TKIs)的风险信号,为该类药品的临床安全用药提供参考。方法使用OpenVigil 2.1数据平台,获取FAERS数据库中4种METTKIs从FDA批准上市起至2024年7月1日的药品不良事件(ADE)报告数据。采用比例失衡法中的报告比值比法(ROR)和比例报告比值比法(PRR)进行数据挖掘,利用《国际医学用语词典》(23.1版)中药物不良反应术语集的首选系统器官分类(SOC)和首选术语(PT)对挖掘到的风险信号进行分类和描述。结果共挖掘出4种MET-TKIs卡马替尼、特泊替尼、克唑替尼和卡博替尼为首要怀疑药物的ADE报告分别为2109、319、9272、22902例,去除产品问题、社会环境、各类损伤、中毒、操作并发症和各种手术及医疗操作等无关信号后获得阳性信号数分别为63、41、64、407个,共累及SOC分别为14、10、16、19个。4种MET-TKIs累及的SOC存在一定的差异,如卡博替尼在“皮肤及皮下组织类疾病”的ADE信号及克唑替尼在“眼器官疾病”均远多于其他3种MET-TKIs。其相同之处主要集中在“全身性疾病及给药部位各种反应”“胃肠系统疾病”和“呼吸系统、胸及纵隔疾病”。本研究还挖掘到说明书中未收录的ADE,如卡马替尼和特泊替尼引起的耳聋、克唑替尼引起的肺水肿、卡博替尼引起的间质性肺疾病等。结论本研究获得的常见ADE信号与说明书具有一定的一致性,证明了该研究方法的可靠性。临床应用该类药物时应注意对其ADE的监测,并警惕说明书未提及的ADE信号,及时采取防治措施,确保临床用药安全。Objective To mine risk signals for four mesenchymal-epithelial transition factor tyrosine kinase inhibitors(MET-TKIs)using the Food and Drug Administration Adverse Event Reporting System(FAERS)database,and provide reference for the clinical safety of these medications.Methods The adverse event(ADE)reports for four MET-TKIs were extracted from the FAERS database using the OpenVigil 2.1 platform,covering data from FDA approval up to July 1,2024.The data mining was performed using the reporting odds ratio(ROR)and the proportional reporting ratio(PRR)methods.The risk signals were classified and described based on the preferred system organ classification(SOC)and preferred terms(PT)from the International Medical Dictionary(version 23.1).Results A total of 2109,319,9272 and 22902 ADE reports were identified for 4 MET-TKIs capmatinib,tepotinib,crizotinib and cabozantinib,respectively.After excluding unrelated signals such as product issues,social environment factors,various injuries,poisoning,procedural complications,and medical operations,63,41,64 and 407,positive signals were found,respectively,involving SOCs of 14,10,16 and 19.The notable differences were observed in the SOCs affected by the four MET-TKIs.For instance,cabozantinib had more ADE signals related to“skin and subcutaneous tissue disorders”,while crizotinib showed higher occurrences in“eye disorders”compared to the other three MET-TKIs.Similarities among the drugs were noted in“systemic disorders and administration site reactions”,“gastrointestinal disorders”,and“respiratory,thoracic,and mediastinal disorders”.The study also identified ADE not included in the product labeling,such as hearing loss with capmatinib and tepotinib,pulmonary edema with crizotinib,and interstitial lung disease with cabozantinib.Conclusion The common ADE signals identified in this study are consistent with those in the product labeling,confirming the reliability of the research methods.Clinicians should monitor ADEs when using these drugs and remain vigilant fo

关 键 词：间质-上皮转换因子酪氨酸激酶抑制剂 美国食品药品监督管理局不良事件报告系统 不良事件信号挖掘 比例失衡法 药物警戒 

分 类 号：R969[医药卫生—药理学]