基于FAERS数据库的肿瘤坏死因子抑制剂不良反应信号的挖掘与分析  

Mining and analysis of tumor necrosis factor inhibitors related adverse drug reaction signals based on the FDA Adverse Event Reporting System

作　　者：张灿华 苏健芬 徐朗 林劲伟 房瑶 郭茵 付喜花 唐郁宽 彭新生 ZHANG Canhua;SU Jianfen;XU Lang;LIN Jinwei;FANG Yao;GUO Yin;FU Xihua;TANG Yukuan;PENG Xinsheng(College of Pharmacy,Guangdong Medical University,Dongguan 523808,China;Department of Pharmacy,Guangzhou Panyu Central Hospital,Guangzhou 511400,China;Department of Pharmacy,Qingyuan Hospital Affiliated to Guangzhou Medical University/Qingyuan People’s Hospital,Qingyuan 511518,China;Department of Anaesthesia,Qingyuan Hospital Affiliated to Guangzhou Medical University/Qingyuan People’s Hospital,Qingyuan 511518,China;Department of Infectious Disease,Guangzhou Panyu Central Hospital,Guangzhou 511400,China;Department of Minimally Invasive Intervention,Guangzhou Panyu Central Hospital,Guangzhou 511400,China)

机构地区：[1]广东医科大学药学院,东莞523808 [2]广州市番禺区中心医院药学部,广州511400 [3]广州医科大学附属清远医院/清远市人民医院药学部,清远511518 [4]广州医科大学附属清远医院/清远市人民医院麻醉科,清远511518 [5]广州市番禺区中心医院感染科,广州511400 [6]广州市番禺区中心医院微创介入科,广州511400

出　　处：《中国临床药学杂志》2024年第5期362-370,共9页Chinese Journal of Clinical Pharmacy

基　　金：广东省教育厅研究生教育创新计划项目(编号2023ANLK_046);广州市科技计划民生科技项目(编号202103000002);广州市科技计划基础与应用基础研究项目(编号201904010065);广州市民生科技攻关计划项目(编号201903010016);广州市番禺区中心医院院内科研基金(编号2021Y001)。

摘　　要：目的 基于美国FDA不良事件报告系统(FAERS)数据库对英夫利西单抗、依那西普、阿达木单抗、培塞利珠单抗、戈利木单抗5种肿瘤坏死因子抑制剂(TNFi)进行药物不良反应(ADR)信号挖掘,为临床合理安全使用TNFi提供参考。方法 从FAERS数据库中收集2004年第1季度至2023年第3季度共79个季度的数据,采用报告比值比(ROR)法和比例报告比值(PRR)法对5种TNFi的ADR报告数据进行信号挖掘,利用《国际医学用语词典》25.0版规范进行汉化及系统分类,并对结果进行分析。结果 获得以5种TNFi为首要怀疑药品的共1 325 026例病例,其中英夫利西单抗158 971例,依那西普497 224例,阿达木单抗559655例,培塞利珠单抗68365例,戈利木单抗40811例,共涉及24个系统和器官分类,主要集中于感染及侵染类疾病、全身性疾病和给药部位的各种反应,以及各种肌肉骨骼及结缔组织疾病,同时也发现了多个药品说明书中未收录的ADR,如依那西普导致的胎儿畸形和失眠等。结论 5种TNFi的ADR主要为感染及侵染类疾病(注射部位痛、注射部位红斑和注射部位肿胀等)、全身性疾病和给药部位的各种反应(鼻咽炎、鼻窦炎和尿路感染等),临床使用TNFi时需重点关注。AIM To guide the rational and safe use of tumor necrosis factor inhibitors(TNFi)through mining and analyzing the adverse drug reaction(ADR)signals of TNFi in the FDA Adverse Event Reporting System(FAERS).METHODS A total of 79 quarters of FAERS data were downloaded from the first quarter of 2004 to the third quarter of 2023 and 5 TNFi-related adverse events were extracted.The reporting odd ratio(ROR)and proportional reporting ratio(PRR)methods were used to detect the ADR signals.The Chinese and systematic classification was carried out according to the Medical Dictionary for Regularly Activities version 25.0(MedDRA),and the results were analyzed.RESULTS There were 1325026 patients with 5 kinds of TNFi as the primary suspected drugs,including 158971 of infliximab,497224 of etanercept,559655 of adalimumab,68365 of certolizumab pegol and 40811 of golimumab,involving a total of 24 system organ classes,mainly focusing on infections and infestations,general disorders and administration site conditions,as well as musculoskeletal and connective tissue disorders,and some new ADRs were discovered,such as fetal malformation and insomnia caused by etanercept.CONCLUSION In this study,we found that the ADRs of these 5 TNFi were mainly distributed in infections and infestations(e.g.injection site pain,injection site erythema,injection site swelling,etc.),and general disorders and administration site conditions(e.g.nasopharyngitis,sinusitis,and urinary tract infection,etc.).These findings highlight the importance of paying attention to these p otential ADRs when clinically using TNFi.

关 键 词：肿瘤坏死因子抑制剂 药物不良反应 FAERS数据库 信号挖掘与分析 报告比值法 比例报告比值法 

分 类 号：R730[医药卫生—肿瘤]