美国不良事件报告系统中丝氨酸/苏氨酸蛋白激酶/丝裂原活化蛋白激酶联合抑制剂不良反应信号数据挖掘与分析  

Data mining and analysis of adverse drug reaction signals for combined serine/threonine-protein kinase B-raf/mitogen-activated protein kinases inhibitors in the U.S.FDA Adverse Event Reporting System

作　　者：刘红[1] 王文娟 白羽[1] 张关敏[1] 张艳华[1] LIU Hong;WANG Wen-juan;BAI Yu;ZHANG Guan-min;ZHANG Yan-hua(Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Pharmacy,Peking University Cancer Hospital&Institute,Beijing 100142,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所药剂科,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142

出　　处：《中国新药杂志》2024年第20期2178-2184,共7页Chinese Journal of New Drugs

摘　　要：目的:本研究旨在比较维莫非尼联合考比替尼、达拉非尼联合曲美替尼和康奈非尼联合贝美替尼3种丝氨酸/苏氨酸蛋白激酶(serine/threonine-protein kinase B-raf,BRAF)/丝裂原活化蛋白激酶(mitogen-activated protein kinases,MEK)联合抑制剂间药品不良反应(adverse drug reaction,ADR)的差异,以期指导临床安全用药。方法:收集2011年第1季度—2023年第2季度美国FDA不良事件报告系统中的ADR报告,使用报告比值比法和贝叶斯可信区间递进神经网络法进行数据分析,同时采用Chi-square统计方法对组间数据进行分析。结果:研究共纳入17982份ADR报告,其中达拉非尼联合曲美替尼报告数最多,为12746份,且报告死亡结局的比例(26.62%)也高于其他方案组。3种治疗方案主要累及系统器官分别为皮肤及皮下组织类疾病、全身性疾病及给药部位各种反应和胃肠系统疾病。在维莫非尼联合考比替尼和康奈非尼联合贝美替尼方案中,浆液性视网膜病关联性最强,维莫非尼联合考比替尼方案发生器质性脑综合征ADR致死概率为100.00%。结论:临床上应关注维莫非尼联合考比替尼方案发生器质性脑综合征ADR致死风险,不同BRAF/MEK联合抑制剂与特定系统器官的ADR关联强度存在差异,临床医生可根据患者的具体需求合理选择药物,并对ADR进行有效监测。Objective:To assess the differences in adverse drug reactions(ADR)across three BRAF/MEK inhibitor combinations,vemurafenib with cobimetinib,dabrafenib with trametinib,and encorafenib with binimetinib thus to improve clinical medication safety.Methods:ADR reports were collected from the U.S.FDA Adverse Event Reporting System from the first quarter of 2011 to the second quarter of 2023.Data analysis was conducted using the reporting odds ratio,Bayesian confidence propagation neural network method,and chi-square tests for inter-group comparisons.Results:The analysis included 17982 ADR reports.Dabrafenib in combination with trametinib had the highest number of reports(12746)and the highest proportion of mortality outcomes(26.62%)compared to other combinations.The primary adverse effects involved systemic organs,including skin and subcutaneous tissue disorders,systemic diseases,reactions at the administration site,and gastrointestinal system diseases.Notably,strong associations were found between serous retinopathy and both the vemurafenib with cobimetinib and encorafenib with binimetinib combinations.The fatal probability of organic brain syndrome ADR in the vemurafenib combined with cobimetinib regimen was 100.00%.Conclusion:Clinicians should be particularly cautious of the risk of death from organic brain syndrome ADR in the vemurafenib combined with cobimetinib regimen.Variation exists in the strength of associations between different BRAF/MEK inhibitor combinations and ADR affecting specific systemic organs.Clinicians should select appropriate therapeutic strategies based on individual patient needs and effectively monitor ADR.

关 键 词：药物警戒 药品不良反应 丝氨酸/苏氨酸蛋白激酶 丝裂原活化蛋白激酶 抑制剂 

分 类 号：R969.3[医药卫生—药理学]