基于美国FAERS的奥希替尼致心脏毒性的风险分析

Analysis of the risks of cardiotoxicity induced by osimertinib based on FAERS Database

目的基于美国FDA不良事件报告系统(FDA Adverse Event Reporting System,FAERS),比较奥希替尼与第一、二代EGFR-TKIs及其他所有药物引起心脏毒性的风险。方法下载FAERS数据库中2015年第4季度至2020年第4季度上报的奥希替尼及背景药物心脏不良事件,采用报告比值比法(Reporting odds ratio,ROR)和比例报告比值比法(Proportional reporting ratio,PRR)进行安全性信号检测。结果根据FAERS数据库,所有与奥希替尼相关的不良事件中,6.6%与心脏有关。与第一、二代EGFR-TKIs相比,奥希替尼发生心衰、心电图QT间期延长、房颤的ROR和PRR(95%CI)分别为1.9(1.5~2.4)和1.9(1.5~2.3),5.6(3.6~8.9)和5.6(3.5~8.8),1.9(1.3~2.8)和1.9(1.3~2.7),均产生不良反应信号。与其他所有药物相比,奥希替尼发生心衰、心电图QT间期延长、房颤、心肌梗死、心包积液的ROR(95%CI)和PRR(95%CI)分别为7.8(6.7~9.1)和7.6(6.6~8.9),9.4(7.7~11.4)和9.3(7.6~11.3),2.6(2.1~3.4)和2.6(2.1~3.3),1.5(1.1~1.9)和1.5(1.1~1.9),8.0(6.0~10.7)和8.0(6.0~10.6),均产生不良反应信号。结论基于FAERS数据库,奥希替尼较第一、二代EGFR-TKIs及其他所有药物引起心脏系统不良事件的风险高,值得引起临床关注。

Objective To compare the risk of cardiotoxicity of osimertinib versus first-and second-generation EGFR-TKIs and versus all other drugs,based on U.S.Food and Drug Administration Adverse Events Reporting System(FAERS).Methods The cardiotoxicity events of osimertinib and background drugs reported in the FAERS database from the fourth quarter of 2015 to the fourth quarter of 2020 were downloaded.The safety signal detection was conducted by using reporting odds ratio(ROR)and proportional reporting ratio(PRR)methods.Results Based on the FAERS database,6.6%of all adverse events related to osimertinib were cardiotoxicity.The ROR(95%CI)and PRR(95%CI)for cardiac failure,QT prolongation and atrial fibrillation due to osimertinib versus first-and second-generation EGFR-TKIs in FAERS was 1.9(1.5~2.4)and 1.9(1.5~2.3),5.6(3.6~8.9)and 5.6(3.5~8.8),1.9(1.3~2.8)and 1.9(1.3~2.7),all generating adverse reaction signals,respectively.The ROR(95%CI)and PRR(95%CI)for cardiac failure,QT prolongation,atrial fibrillation,myocardial infarction and pericardial effusiondue due to osimertinib versus all other drugs in FAERS was 7.8(6.7~9.1)and 7.6(6.6~8.9),9.4(7.7~11.4)and 9.3(7.6~11.3),2.6(2.1~3.4)and 2.6(2.1~3.3),1.5(1.1~1.9)and 1.5(1.1~1.9),8.0(6.0~10.7)and 8.0(6.0-10.6),all generating adverse reaction signals,respectively.Conclusion Based on the FAERS database,the risk of cardiotoxicity of osimertinib versus the first and second generation EGFR-TKIs and versus all other drugs is higher,which deserves clinical attention.