基于美国FDA公共数据开放项目数据库的别嘌醇和非布司他风险信号的挖掘和比较  

Mining and comparation on the risk signals related to allopurinol and febuxostat based on the US Food and Drug Administration Public Data Open Project database

作　　者：张美娟 尹航[1] 李江硕 侯梦雨 吴竞轩 董瑞华 Zhang Meijuan;Yin Hang;Li Jiangshuo;Hou Mengyu;Wu Jingxuan;Dong Ruihua(Department of Research Ward,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院研究型病房,北京100050

出　　处：《药物不良反应杂志》2023年第8期460-468,共9页Adverse Drug Reactions Journal

基　　金：北京市研究型病房建设示范单位项目(BCRW202010);中国毒理学会临床毒理专项(CST2020CT301)。

摘　　要：目的挖掘并分析比较降尿酸药别嘌醇和非布司他不良事件(AE)信号,为临床合理安全使用该两种药品提供参考。方法检索美国食品药品管理局公共数据开放项目(openFDA)数据库,收集2009年1月1日至2021年12月31日以别嘌醇和非布司他为目标药物的AE报告,采用国际医学用语词典25.0版首选术语(PT)和系统器官分类(SOC)对AE进行标准化和分类。采用报告比值比(ROR)法挖掘别嘌醇和非布司他风险信号,报告数≥3、ROR的95%置信区间下限>1定义为阳性信号。对照药品说明书筛选别嘌醇和非布司他新的AE风险信号,按照别嘌醇和非布司他的风险信号数量绘制雷达图,对阳性PT信号进行描述性分析。结果别嘌醇和非布司他AE报告分别为105532和9949份。对报告数量排前100位AE分析的结果显示,别嘌醇阳性PT 82个,涉及14个SOC,药品说明书中未记载的AE为61个;非布司他阳性PT 86个,涉及18个SOC,药品说明书中未记载的AE为25个。别嘌醇信号强度居前5位的PT为药物反应伴嗜酸粒细胞增多和全身性症状、终末期肾脏疾病、高钙血症、急性肾损伤、慢性肾脏疾病;非布司他信号强度居前5位的PT为起止点病、皮肤肉芽肿、血甲状旁腺素降低、腱鞘炎、丙氨酸氨基转移酶异常。两药共有重叠信号49个,别嘌醇在代谢及营养类疾病、血液和淋巴系统疾病等SOC检测到的风险信号种类较多,非布司他在皮肤及皮下组织类疾病、各种肌肉骨骼及结缔组织疾病等SOC检测到的风险信号种类较多。结论别嘌醇致肾脏和泌尿系统、血液和淋巴系统及代谢系统相关AE的风险较高,非布司他致皮肤及皮下组织、肌肉骨骼及结缔组织、肝胆系统相关AE的风险较高。建议伴有肾功能不全、泌尿系统疾病或血液系统疾病的痛风患者慎用别嘌醇,伴有肝功能异常的痛风患者慎用非布司他。Objective To mine and compare the adverse event(AE)signals of allopurinol and febuxostat and provide reference for the rational and safe use of the 2 drugs in clinic.Methods The AE reports on allopurinol and febuxostat from January 1,2009 to December 31,2021 were collected by searching the US Food and Drug Administration Public Data Open Project(openFDA)database.AEs were classified using preferred term(PT)and systemic organ class(SOC)of the International Medical Terminology Dictionary 25.0.The AE risk signals of allopurinol and febuxostat were mined using the reporting odds ratio(ROR)method.The number of AE reports≥3 and the lower limit of the 95%confidence interval(CI)of the ROR>1 was defined as a positive signal.The new AE risk signals of allopurinol and febuxostat were screened according to the drug labels.The radar chart was drawn according to the number of allopurinol and febuxostat risk signals.The positive PT signals were descriptively and statistically analyzed.Results The number of AE reports of allopurinol and febuxostat were 105532 and 9949,respectively.The analysis of the top 100 AE reports were as follows.There were 82 positive PT signals of allopurinol,involving 14 SOCs,and 61 AEs were not recorded in the drug labels;there were 86 positive PT signals of febuxostat,involving 18 SOCs,and 25 AEs were not recorded in the drug labels.The top 5 PTs in the signal strength of allopurinol were drug reaction with eosinophilia and systemic symptoms,end‑stage renal disease,hypercalcemia,acute kidney injury,and chronic kidney disease;the top 5 PTs in the signal strength of febuxostat were enthesopathy,granuloma skin,blood parathyroid hormone decreased,tenosynovitis and alanine aminotransferase abnormal.The 2 drugs had a total of 49 overlapping signals.More AE signals of allopurinol were detected in SOCs of metabolic and nutritional diseases,blood and lymphatic system diseases etc.;more AE signals of febuxostat were detected in SOCs of skin and subcutaneous tissue diseases,various musculoskeletal,and connecti

关 键 词：痛风 抗痛风药 别嘌醇 非布司他 不良事件 openFDA 安全性 

分 类 号：R97[医药卫生—药品]