基于FAERS数据库对第三代表皮生长因子受体酪氨酸激酶抑制剂奥希替尼的不良反应信号挖掘研究  

Signal mining study of third-generation EGFR-TKI olmutinib based on adverse reaction signals from FAERS database

作　　者：王紫灏 闫森[1] WANG Zi-hao;YAN Sen(Department of Pharmacy,Sanmenxia Yellow River Hospital,Sanmenxia 472000,China)

机构地区：[1]黄河三门峡医院药学部,三门峡472000

出　　处：《中国新药杂志》2025年第8期891-896,共6页Chinese Journal of New Drugs

摘　　要：目的:对表皮生长因子受体(epidermal growth factor receptor,EGFR)-酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKl)奥希替尼(olmutinib)不良反应(adverse reaction,ADR)信号进行挖掘分析,为临床安全合理用药提供参考。方法:收集美国FDA不良事件报告系统(FAERS)数据库2012年10月—2023年6月的奥希替尼不良事件报告(adverse event reports,ADE)。从逐年呈报趋势、患者的性别及年龄、严重不良事件等角度对上述药品不良事件报告进行统计描述。采用比例失衡法中的报告比值比法(reporting ratio ratio,ROR)、比例报告比值比法(proportionate reporting ratio,PRR)、贝叶斯置信度递进神经网络法(Bayesian confidence progressive neural network,BCPNN)对FAERS数据库的数据进行数据挖掘和分析,检测上述药物的安全信号,并分析重点累及器官和高危信号。结果:共收集到以奥希替尼为首要怀疑(the first suspected,PS)药物的ADR报告63726例,其中女性患者(66.0%)高于男性患者(27.7%),并且主要集中在18~44岁(23.8%)、60~74岁(19.2%)和≥75岁(19.2%)这3个年龄段,易发生死亡(40.09%)、住院(20.80%)等严重ADE。应用3种数据挖掘法检测出共同阳性信号386个,奥希替尼累及器官/系统前5的分别是胃肠系统疾病(11.1%)、呼吸系统及胸纵隔疾病(10.1%)、各类检查-医学检查指标异常(9.3%)、各类神经系统疾病(7.0%)和皮肤及皮下组织类疾病(6.2%),信号强度前5的ADR分别为消化道水肿(BCPNN 95%CI=7.07)、急性早幼粒细胞白血病(BCPNN 95%CI=7.05)、葡萄膜炎(BCPNN 95%CI=6.78)、鼻窦疾病(BCPNN 95%CI=6.43)和EGFR基因突变(BCPNN 95%CI=6.36)。结论:奥希替尼可引起消化系统、呼吸系统、各类神经系统等疾病症状,临床医务工作者在治疗期间应密切关注,还应关注奥希替尼信号较强和新的ADR(消化道水肿、急性早幼粒细胞白血病)、严重的ADE(死亡、住院等),并且关注女性患者和重点年龄人群。Objective:To mine and analyze adverse reaction signals of olmutinib,an epidermal growth factor receptor(EGFR)tyrosine kinase inhibitor(TKl),for safe and rational clinical use.Methods:Adverse event reports of olmutinib from October 2012 to June 2023 were collected from the FAERS database,the adverse event reporting system of the U.S.FDA.The adverse drug event(ADE)reports were statistically described from the perspectives of year-to-year presentation trends,gender and age of patients,and serious adverse events as described above.The data were mined and analyzed using reporting odds ratio(ROR),proportionate reporting ratio(PRR),and Bayesian confidence progressive neural network(BCPNN)methods of the proportional imbalance method to detect the safety signals of olmutinib and analyze the key involved organs and high-risk signals.Results:A total of 63726 reports of adverse reactions were collected with olmutinib as the first suspected(PS)drug,among which female patients had higher percentage(66.0%)than male patients(27.7%).The reports mainly concentrated in the age groups of 18~44 years(23.8%),60~74 years(19.2%),and≥75 years(19.2%),and included cases susceptible to death(40.09%),hospitalization(20.80%),and other serious adverse effects.Three data mining methods were applied to detect 386 co-positive signals,and the top five cumulative organs of olmutinib were gastrointestinal diseases(11.1%),respiratory and thoracic mediastinum diseases(10.1%),abnormalities in the indicators of various examinations and medical tests(9.3%),all kinds of neurological diseases(7.0%),and diseases of the skin and subcutaneous tissues(6.2%),and the top five ADRs in signal intensity were gastrointestinal edema(BCPNN 95%CI=7.07),acute promyelocytic leukemia(BCPNN 95%CI=7.05),uveitis(BCPNN 95%CI=6.78),sinus disease(BCPNN 95%CI=6.43),and EGFR gene mutation(BCPNN 95%CI=6.36).Conclusion:Olmutinib can cause symptoms of gastrointestinal system and respiratory system,as well as various types of neurological disorders,which should be closely monitored

关 键 词：奥希替尼 数据挖掘 比例失衡算法 

分 类 号：R969.3[医药卫生—药理学]