基于FDA不良事件数据库对伊立替康和氟尿嘧啶安全信号的挖掘与分析

Mining and analysis of irinotecan and fluorouracil safety signals based on FDA adverse event database

目的挖掘和分析伊立替康与氟尿嘧啶的安全信号。方法选取2004年1月至2021年9月美国FDA不良事件报告系统(FDA adverse event reporting system,FAERS)收录的以伊立替康和氟尿嘧啶为怀疑对象的不良反应(adverse drug reaction,ADR)报告。采用报告比值和比例报告信号检测方法对其进行ADR信号检测。结果初次筛选,伊立替康、氟尿嘧啶及二药联合用药分别得到583、1239以及674个首选术语(preferred term,PT)。二药联合用药报告数量排序前3的PT分别是腹泻(5.88%)、中性粒细胞减少(3.41%)以及恶心(3.26%)。二次筛选后,伊立替康、氟尿嘧啶及二药联合用药分别得到28、70以及60个PT,分别累及10、17以及13个系统器官分类。在二药联合应用中经二次筛选过的PT胆碱能综合征报道比值为127.4,95%置信区间为(82.9,195.6)。通过对比初次筛选和二次筛选的维恩图,伊立替康、氟尿嘧啶及二药联合用药之间信号较突出的PT重叠度明显减少。结论使用单药时,ADR的发生情况较为突出。

Objective To explore and analyze the safety signals of irinotecan and fluorouracil.Methods The adverse drug reaction(ADR)reports with irinotecan and fluorouracil as suspects included in the FDA adverse event reporting system(FAERS)from January 2004 to September 2021 were selected.The ADR signals were detected by reporting odds ratio and proportional reporting signals.Results For the primary screening,583,1239 and 674 preferred term(PT)were obtained by irinotecan,fluorouracil and the combination of two drugs,respectively.The top 3 PT in the number of reports of the combination of two drugs were diarrhea(5.88%),neutropenia(3.41%)and nausea(3.26%),respectively.After secondary screening,28,70 and 60 PT were obtained by irinotecan,fluorouracil and the combination of two drugs,and 10,17 and 13 system organ class were involved,respectively.In the double-screened PT cholinergic syndrome,the reporting odds ratio was 127.4 and 95%confidence interval was(82.9,195.6).By comparing the Venn diagram of primary screening and secondary screening,the overlap of PT with prominent signal was significantly reduced among irinotecan,fluorouracil and the combination of two drugs.Conclusion When using single drug,ADR is more prominent.