FAERS中免疫检查点抑制剂相关严重皮肤不良反应数据挖掘

Data mining of severe cutaneous adverse reactions related to immune checkpoint inhibitors in the FAERS

目的 挖掘并分析5种常用免疫检查点抑制剂(ICIs)相关严重皮肤不良反应信号,为临床安全用药提供参考。方法 从美国FDA不良事件报告系统(FAERS)数据库中收集伊匹木单抗、纳武利尤单抗、帕博利珠单抗、阿替利珠单抗和度伐利尤单抗自美国上市至2022年第4季度相关严重皮肤不良反应的药物不良事件(ADEs)报告,采用报告比值比(ROR)法和贝叶斯置信区间递进神经网络(BCPNN)法对信号进行挖掘与分析。结果 共收集到严重皮肤不良反应报告5 726份,其中纳武利尤单抗3 037份、帕博利珠单抗1 465份、度伐利尤单抗130份、阿替利珠单抗429份、伊匹木单抗665份。5种ICIs均生成了阳性信号,其关联度由强到弱依次是帕博利珠单抗>阿替利珠单抗>纳武利尤单抗>伊匹木单抗>度伐利尤单抗。5种ICIs均有报告史-约综合征和中毒性表皮坏死松解症发生,关联度均以帕博利珠单抗最强。结论 5种ICIs均有导致严重皮肤不良反应发生的风险,临床在使用时应密切关注,尤其在使用帕博利珠单抗时应特别谨慎;同时,应尽量避免ICIs之间的联用。

OBJECTIVE To mine and analyze severe cutaneous adverse reaction signals of 5 commonly used immune checkpoint inhibitors(ICIs),and to provide reference for clinically safe use of drugs.METHODS Based on the FDA adverse events reporting system(FAERS)database,adverse drug events(ADEs)reports about severe cutaneous adverse reactions related to ipilimumab,nivolumab,pembrolizumab,atezolizumab and durvalumab were collected from listing in the United States to the fourth quarter of 2022.The ADE signals were mined and analyzed with reporting odds ratio(ROR)and Bayesian confidence propagation neural network(BCPNN).RESULTS A total of 5726 reports of severe cutaneous adverse reactions were collected,including 3037 reports for nivolumab,1465 reports for pembrolizumab,130 reports for durvalumab,429 reports for atezolizumab and 665 reports for ipilimumab.All 5 kinds of ICIs caused positive signals,the correlation degree of which was as follows:pembrolizumab>atezolizumab>nivolumab>ipilimumab>durvalumab.Stevens-Johnson syndrome(SJS)and toxic epidermal necrolysis(TEN)have been reported for all 5 ICIs,and the association was the strongest with pembrolizumab.CONCLUSIONS All 5 kinds of ICIs are associated with the risk of severe skin adverse reactions,and close attention should be paid to their clinical use,especially being cautious when using pembrolizumab.The combination of ICIs should be avoided as much as possible.