基于FAERS的索拉非尼药品不良事件信号挖掘

Signal Mining of Adverse Drug Events of Sorafenib Based on FAERS Database

目的挖掘索拉非尼的药品不良事件(ADE)信号,促进索拉非尼的临床安全应用。方法检索美国食品和药物管理局不良事件报告系统(FAERS)中2006年第一季度至2022年第四季度有关索拉非尼的ADE报告,采用报告比值比(ROR)法和英国药品和保健品管理局(MHRA)综合标准法进行信号检测,采用国际医学用语词典中的首选语(PT)及系统器官分类(SOC)进行编码和归类。结果共检索到以索拉非尼为首要怀疑药物的ADE报告17838份(涉及患者17838例次),共报告ADE 77033项。经ROR法和MHRA综合标准法检测,共筛选出ADE信号29880项,累计PT 375个,涉及21个SOC。ADE信号报告数最多的SOC为皮肤及皮下组织类疾病(7557项),强度最强的为维生素K缺乏或拮抗剂Ⅱ诱导产生的蛋白升高(ROR的95%置信区间下限=181.29)。结论目前的索拉非尼药品说明书中对不良反应的表述尚不全面,而该药的临床应用较广泛,且较新的临床研究较少,该研究补充了药品说明书中未收录但真实世界中信号较强的ADE,为该药的药物警戒工作及临床用药提供了参考。

Objective To mine the adverse drug event(ADE)signals of sorafenib,and to promote the safe clinical application of sorafenib.Methods The ADE reports of sorafenib from the first quarter of 2006 to the fourth quarter of 2022 were extracted from the US Food and Drug Administration Adverse Event Reporting System(FAERS)database.The reporting odds ratio(ROR)method and the Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive method were used to mine the signals.The preferred terms(PT)and system organ classification(SOC)in the MedDRA were used for encoding and classification.Results A total of 17838 reports(involving 17838 patients)were retrieved with sorafenib as the primary suspected drug,and 77033 ADEs were reported.Through ROR and MHRA comprehensive methods,29880 ADE signals were screened,with a cumulative total of 375 PTs and 21 SOCs involved.The SOC with the highest number of reported ADE signals was skin and subcutaneous tissue diseases(7557 items),and the ADE with the strongest signal was the protein elevation induced by vitamin K absence or antagonistⅡ(ROR 95%CI lower limit=181.29).Conclusion The description of adverse reactions in the drug instructions of sorafenib is not comprehensive,and the clinical application of this drug is relatively extensive,while the new clinical studies are few.This study supplements ADEs that are not included in the drug instructions but have strong signals in the real world,which provids a reference for the pharmacovigilance work and clinical use of sorafenib.