基于美国食品药品监督管理局不良事件报告系统数据库的阿普斯特不良事件信号挖掘与分析

Signal mining and analysis of adverse drug events for apremilast based on FAERS database

目的基于美国食品药品监督管理局(FDA)不良事件报告系统(FAERS)数据库挖掘阿普斯特的安全警戒信号,为临床安全使用提供参考。方法以药品通用名“Apremilast”、商品名“Otezla”和别名“CC-10004”为关键词,通过FDA FAERS数据库检索阿普斯特自上市以来(2014年第二季度至2022年第四季度)的药物不良事件(ADE)信号。应用报告比值比法(ROR)和贝叶斯置信度递进神经网络法(BCPNN)对信号进行挖掘与分析。结果阿普斯特ADE报告共118818份,其中女性75134例(63.23%);年龄主要集中在19~64岁48917例(41.17%);数据上报人员主要为药师40779例(34.32%);美国为主要上报国家(94.12%)。筛选出ADE信号共3620个,排除非药物因素的信号后,排名前十位的分别是腹泻、恶心、银屑病、头痛、腹部不适、银屑病关节炎、呕吐、抑郁、体质量降低、皮疹。ADE信号共涉及27个系统器官分类,主要为胃肠系统疾病(62454例),全身性疾病及给药部位各种反应(37214例),皮肤与皮下组织类疾病(29823例),各类神经系统疾病(22623例),各类损伤、中毒及操作并发症(16711例)及各种肌肉骨骼与结缔组织疾病(16292例)等。结论阿普斯特治疗过程中,应关注患者有无胃肠系统不适症状,药物无效与银屑病复发等ADE。同时应评估患者精神疾病发生风险,开始治疗后,密切监测患者精神疾病有无恶化,有无自杀或其他异常行为。

Objective To mine the safety warning signals of apremilast based on the database of the US FDA Adverse Event Reporting System(FAERS),so as to provide reference for clinical safe use.Methods With the generic drug name"Apremilast",trade name"Otezla",and alias"CC-10004"as keywords,the adverse drug events(ADE)signals of apremilast since its listing(from the second quarter of 2014 to the fourth quarter of 2022)were retrieved through the FAERS database.The reporting odds ratio(ROR)and bayesian confidence propagation neural network(BCPNN)were used to mine and analyze the signals.Results A total of 118818 ADE reports from apremilast were retrieved,including 75134 female cases,accounting for 63.23%.The age of patients in ADE report was mostly 19-64 years old(48917 cases,accounting for 41.17%).These data were mainly reported by pharmacists(40779 copies,accounting for 34.32%).The United States was the main reporting country(accounting for 94.12%).A total of 3620 ADE signals were screened out.After excluding the signals of non-drug factors,the top ten ADE signals were diarrhea,nausea,psoriasis,headache,abdominal discomfort,psoriatic arthritis,vomiting,depression,weight loss and rash.All selected ADE signals involved 27 system organ classes(SOC),the main dis-eases of which were Gastrointestinal diseases(62454 cases),General disorders and administration site conditions(37214 cases),Skin and subcutaneous tissue disorders(29823 cases),Nervous system disorders(22623 cases),Injury,poisoning and procedural complications(16711 cases),and Musculoskeletal and connective tissue disor-ders(16292 cases).Conclusion During the treatment of apremilast,special attention should be paid to whether the patients have symptoms of the drug-induced ADE in gastrointestinal discomfort,drug ineffectiveness and psori-asis recurrence.At the same time,the risk of mental illness should be assessed.After starting the treatment,the patients'mental illness should be closely monitored for deterioration,suicide or other abnormal behavior.