基于OpenVigil对索拉非尼和瑞戈非尼不良事件的信号挖掘与分析★

Research on signal mining of adverse events of sorafenib and regorafenib based on OpenVigil★

摘要:

目的 对索拉非尼和瑞戈非尼两种多激酶抑制剂进行药品不良事件（ADE）信号挖掘和分析评价，为临床用药提供参考。方法 检索OpenVigil 2.1数据库索拉非尼和瑞戈非尼的ADE报告，时间截至2022年第2季度。使用报告比值比法（ROR）、比例报告比法（PRR）和综合标准法（MHRA）进行信号挖掘，评价ADE信号特点。结果 收集到索拉非尼ADE报告11 391例，瑞戈非尼4 941例。ADE信号929个，其中索拉非尼579个，瑞戈非尼350个。索拉非尼报告数最多的是腹泻，有1 363例（11.97%），关联性最强的是维生素K缺乏或拮抗剂Ⅱ诱导产生的蛋白升高（ROR=502.46， PRR=502.064），瑞戈非尼报告数最多的疲劳，有598例（12.1%），关联性最强的是掌跖角化病（ROR=185.378， PRR=185.08）。索拉非尼ADE信号累及系统器官分类（SOC）为25个，瑞戈非尼22个。索拉非尼药品说明书未载明的ADE信号有2种，瑞戈非尼3种。结论 索拉非尼与瑞戈非尼作为结构相似的抗肿瘤药物，筛选得到的ADE信号大多重叠，在报告数、涉及系统器官和关联强度上发现新信号，提示临床使用需注意相关ADE。两种药物ADE信号报告数和关联强度的差异可为其临床使用提供参考，建议临床根据信号偏倚合理使用。

Abstract:

Objective To mine and evaluate the adverse drug event (ADE) signals of sorafenib and regorafenib, so as to provide reference for clinical medication.Methods ADE reports of sorafenib and regorafenib were retrieved in the OpenVigil 2.1 database up to the second quarter of 2022. The reporting odds ratio (ROR), proportional reporting ratio (PRR) and comprehensive standard method (MHRA) were used for signal mining to evaluate the characteristics of ADE signals.Results A total of 11 391 cases of sorafenib ADE and 4 941 cases of regorafenib ADE were reported. There were 929 ADE signals, including 579 for sorafenib and 350 for regorafenib. The ADE most frequently reported for sorafenib was diarrhea, with 1 363 cases (11.97%), and its strongest association was with vitamin K deficiency or antagonist II-induced protein elevation (ROR=502.46, PRR=502.064). As for regorafenib, the most frequently reported ADE was fatigue, with 598 cases (12.1%), and its strongest association was with palmoplantar keratoderma (ROR=185.378, PRR=185.08). Sorafenib ADE signals involved 25 system organ classes (SOCs), while regorafenib ADE signals involved 22 SOCs. Two ADE signals were identified as unmentioned in the sorafenib package insert, and three were found unmentioned in the regorafenib package insert.Conclusion Sorafenib and regorafenib, as structurally similar anti-cancer drugs, have mostly overlapping ADE signals. New signals were found in terms of the number of reports, involved systems and organs, and association strength, suggesting that clinicians should pay attention to the related ADEs. The differences in the number of ADE signal reports and association strength between the two drugs can provide reference for their clinical use, and it is recommended to use them based on signal bias in clinical practice.