基于FAERS数据库对拉替拉韦和多替拉韦的药物不良事件信号挖掘与分析

Signal mining and analysis of adverse drug events of raltegravir and dolutegravir based on the FAERS database

摘要

目的: 基于美国食品药品监督管理局不良事件报告系统(FDA adverse event reporting system,FAERS)数据库挖掘拉替拉韦和多替拉韦的药物不良事件(adverse drug event,ADE)信号,为临床安全用药及合理选药提供参考。方法: 提取FAERS数据库中拉替拉韦2007年第4季度至2024年第4季度、多替拉韦自2013年第3季度至2024年第4季度的ADE报告数据,采用报告比值比法(reporting odds ratio,ROR)和比例报告比法(proportional reporting ratio,PRR)进行数据挖掘。结果: 排除各类损伤、中毒及操作并发症,各类手术及医疗操作,以及产品问题和社会问题等与药物无关的信号后,得到拉替拉韦相关的ADE报告有 4 136 例,有效信号为288个,涉及23个系统器官;多替拉韦相关的ADE报告有2 119例,有效信号为165个,涉及系统器官22个。拉替拉韦和多替拉韦差异较大的相关ADE信号主要集中在各类神经系统疾病、精神类疾病、感染及侵染类疾病、血液及淋巴系统疾病、妊娠期、产褥期及围产期状况、各种先天性家族性遗传性疾病、眼器官疾病等方面,且多替拉韦在各类神经系统疾病和精神类疾病相关ADE具有更高风险,而拉替拉韦在其余疾病相关ADE具有更高风险。结论: 研究发现拉替拉韦与多替拉韦在治疗获得性免疫缺陷综合征时的不良事件发生风险存在较大差异,可为临床个体化治疗提供参考。

Abstract

Objective: To mine the adverse drug event (ADE) signals of raltegravir and dolutegravir based on the FDA adverse event reporting system (FAERS) database, and provide references for clinical medication safety and rational drug selection. Methods: All ADE reports of raltegravir from the fourth quarter of 2007 to the fourth quarter of 2024 and dolutegravir from the third quarter of 2013 to the fourth quarter of 2024 in the FAERS database were mined using reporting odds ratio (ROR) and proportional report ratio (PRR). Results: After excluding all kinds of injuries, poisoning, and operation complications, as well as other unrelated signals such as all kinds of operations and medical operations, product problems and social problems, there were 4 136 ADE reports related to raltegravir, 288 effective signals were obtained, and the signals involved 23 system organs; there were 2 119 cases of dolutegravir-related ADE reports, 165 effective signals were mined, and 22 system organs were involved. The related ADE signals with significant differences between raltegravir and dolutegravir were mainly concentrated in nervous system disorders, psychiatric disorders, infections and infestations, blood and lymphatic system diseases, pregnancy, puerperium and perinatal conditions, congenital, familial and genetic diseases, and eye diseases, etc. Dolutegravir had a higher risk of ADEs in nervous system disorders and psychiatric disorders, while raltegravir had a higher risk in other disease-related ADEs. Conclusion: The study found that there is a significant difference in the risk of adverse events between raltegravir and dolutegravir in the treatment of acquired immunodeficiency syndrome, which can provide references for individualized clinical treatment.

关键词

拉替拉韦 / 多替拉韦 / 获得性免疫缺陷综合征 / 美国食品药品监督管理局不良事件报告系统 / 药物不良事件 / 信号挖掘

Key words

raltegravir / dolutegravir / acquired immune deficiency syndrome / FDA adverse event reporting system / adverse drug event / signal mining

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基金资助

河北省医学科学研究课题计划资助项目(20241004);国家自然科学青年科学基金资助项目(82104288);河北省自然科学基金生物医药联合基金资助项目(H2020307043)