免疫检查点抑制剂致心肌炎风险分析-基于open FDA数据库的真实世界研究

Risk analysis of myocarditis induced by immune checkpoint inhibitors:a real-world study based on the open FDA database

目的对免疫检查点抑制剂(ICI)致心肌炎的临床特征进行分析。方法从美国FDA不良事件报告系统(FAERS)中下载2014年1月1日至2022年9月30日关于ICI(阿替利珠单抗、度伐利尤单抗、帕博利珠单抗和纳武利尤单抗)导致心肌炎的不良反应(ADR)报告。对ICI相关心肌炎患者的性别、年龄、用药剂量、发生时间等进行分析。结果共提取到ICI相关心肌炎ADR报告1892例。ICI致心肌炎患者男性多于女性(1.9∶1)。有糖尿病、心脏病等基础疾病以及65~75岁年龄段患者的发病率较高。纳武利尤单抗使用常规剂量30天的发病率较高,其他3种药物常规使用剂量31~90天发病率较高,联合用药较单药使用的发病率更高。结论不同品种ICI均可导致心肌炎发生,男性、高龄、患有基础疾病和联合用药可能是ICI致心肌炎的风险因素。

Objective To investigate the risk of myocarditis caused by immune checkpoint inhibitors(ICI).Methods The adverse reaction(ADR)reports on myocarditis caused by atelizumab,duvalizumab,pabolizumab,and navulizumab were downloaded from the FDA Adverse Event Reporting System(FAERS)from January 1,2014 to September 30,2022.The relevant analysis was conducted on the gender,age,medication dosage,and occurrence time of ICI related myocarditis patients.Results A total of 1892 reports of myocarditis induced by ICI were included.The proportion of myocarditis caused by ICI was higher in males than in females(1.9∶1).The incidence of myocarditis in patients with basic diseases such as diabetes and heart disease,and in the age group 65-75 was relatively high.The incidence of myocarditis caused by navulizumab was high within 30 days with the use of conventional doses,and that of the other three drugs were high within 31 to 90 days.And the incidence of myocarditis is higher when used in combination than when used alone.Conclusion Different varieties of ICI can lead to the occurrence of myocarditis,and male,elderly,underlying diseases,and combination therapy may be risk factors for myocarditis caused by ICI.