基于FAERS数据库的奥希替尼ADE信号挖掘与耐药性分析  

Signal mining and drug-resistance analysis of Osimertinib ADE based on FAERS database

作　　者：钟国柱 饶秋红 叶淑芳 丘振文[1] ZHONG Guozhu;RAO Qiuhong;YE Shufang;QIU Zhenwen(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Guangzhou Hospital of Integrated Traditional and Western Medicine,Guangzhou 510800,China)

机构地区：[1]广州中医药大学第一附属医院药学部,广东广州510405 [2]广州市中西医结合医院药学部,广东广州510800

出　　处：《广东药科大学学报》2025年第1期33-40,共8页Journal of Guangdong Pharmaceutical University

基　　金：广州市中医药和中西医结合科技项目(20232A011026)。

摘　　要：目的 基于FDA不良事件(adverse drug event, ADE)报告系统数据库(FDA adverse event reporting system,FAERS),挖掘奥希替尼的ADE信号,分析奥希替尼的耐药因素,为临床用药安全提供参考。方法 通过FAERS数据库提取筛选2015年11月―2023年12月奥希替尼ADE报告,采用报告比值比法和英国药品和健康产品管理局综合标准法,挖掘奥希替尼潜在的ADE信号;并将所挖掘的耐药与基因突变信号的PRIMARYID进行匹配,分析奥希替尼耐药与基因突变之间的关联;通过χ2检验分析不同性别和地区耐药患者发生基因突变是否有显著差异。结果共收集到37 188例以奥希替尼为首要怀疑药物的ADE报告,涵盖168个ADE信号,信号强度排名前5的PT分别为获得性基因突变、HER2基因扩增、RET基因突变、BRAF基因突变、TP53基因突变;耐药与基因突变的PRIMARYID匹配度达88%,545名耐药患者中有250名患者同时发生基因突变。χ2检验结果表明,耐药患者是否发生基因突变与性别(P=0.02)和地区(P=0.01)有关(P<0.05)。结论 获得性基因突变、HER2基因扩增、RET基因突变、BRAF基因突变、TP53基因突变等信号与奥希替尼具有极强的关联性,且与FAERS数据库中耐药信号有强关联性。基于FAERS数据库,对于奥希替尼耐药患者,除了考虑性别和地区因素外,还应明确患者基因分型,及时采取治疗措施,保障临床用药安全。Objective To mine the Adverse Drug Event(ADE)signals of osimertinib,and to analyze the drug-resistant factors of osimertinib based on FDA adverse event reporting system(FAERS),which would provide a reference for clinical drug safety.Methods The ADEs of Osimertinib from November 2015 to December 2023 were extracted and screened from FAERS database.The ADE signals of Osimertinib were analyzed and monitored by the reporting odds ratio(ROR)method and the comprehensive standard method of the Medicines and Healthcare products Regulatory Agency(MHRA).The PRIMARYIDs of drug-resistant and gene mutation were matched to analyze the association between Osimertinib resistance and gene mutation.The Chi-square test was used to examine whether there were significant differences in the occurrence of genetic mutations in drug-resistant patients by gender and region.Results A total of 37188 ADE reports were collected with Osimertinib as the primary suspected drug,covering 168 ADE positive signals.The top five PTs in terms of signal intensity were acquired gene mutations,HER2 gene amplification,RET gene mutations,BRAF gene mutations,and TP53 gene mutations.There was an 88 percent PRIMARYID match between drug-resistance and mutations,with 250 of the 545 resistant patients having concurrent gene mutations. The results of the Chi-square test showed that whether thegene mutation occurred in drug-resistant patients was related to gender (P=0.02) and region (P=0.01, P<0.05).Conclusion Acquired gene mutations, HER2 gene amplification, RET gene mutations, BRAF gene mutations andTP53 gene mutations are highly correlated with Osimertinib and strongly correlated with drug-resistant signals inthe FAERS database. Based on the FAERS database, for Osimertinib-resistant patients, in addition to consideringgender and regional factors, the genotyping of patients should be clarified, and timely therapeutic measures shouldbe taken to ensure the safety of clinical medication.

关 键 词：奥希替尼 FAERS数据库 药物不良事件 耐药 基因突变 

分 类 号：R969.3[医药卫生—药理学]