基于FDA不良事件报告系统数据库的别嘌醇和非布司他不良事件信号挖掘研究

Signal Mining Study of Adverse Reaction Associated with Allopurinol and Febuxostat Based on FDA Adverse Events Reporting System(FAERS)Database

目的基于FDA不良事件报告系统数据库对非布司他、别嘌醇进行不良事件信号挖掘,探索其潜在的用药风险,促进临床合理安全用药。方法提取FDA不良事件报告系统数据库2017年第一季度至2022年第二季度共22个季度有关非布司他、别嘌醇的不良事件报告数据,利用ROR法及PRR法对非布司他、别嘌醇不良事件(AE)进行信号挖掘。结果别嘌醇AE报告5060份,集中于≥60岁患者,累及系统器官分类项目(SOC)共计25项,主要累及在皮肤及皮下组织类疾病(40.01%),发现说明书中未累及系统12项,非布司他AE报告905份,累及SOC共计17项,主要累及在心脏器官疾病(40.17%),发现说明书中未累及系统2项。别嘌醇、非布司他累及感染及侵染类疾病(5.51%、0.49%),肝胆系统疾病(5.35%、0.87%),但别嘌醇说明书中均未收录。别嘌醇累及生殖系统及乳腺疾病(0.55%),妊娠期、产褥期及围产期状况(0.03%),但非布司他未发现累及以上SOC。结论别嘌醇较非布司他,说明书收录不良反应较不充分,新发现的累及SOC及AE为完善别嘌醇说明书不良反应可提供参考。研究发现别嘌醇和非布司他累及SOC差异,可为临床个体化治疗提供参考。

Objective To conduct signal mining of adverse events(AEs)of allopurinol and febuxostat based on FAERS database,and to explore their potential drug risks and promote rational and safe clinical drug use.Methods The adverse event report data of febuxostat and allopurinol in 22 quarters from the first quarter of 2017 to the second quarter of 2022 were extracted from FAERS database,and the signal mining of febuxostat and allopurinol adverse events(AE)was carried out using ROR method and PRR method.Results There were 5060 AE reports for allopurinol,concentrated in patients aged≥60 years,involving 25 items of system organ classification(SOC),mainly in skin and subcutaneous tissue diseases(40.01%).It was found that 12 SOC categories were not mentioned in the instructions.For febuxostat,there were 905 AE reports,involving 17 SOC items,mainly in cardiac organ diseases(40.17%),and 2 items were not involved in the instructions.Allopurinol and febuxostat were associated with infection and infectious diseases(5.51%,0.49%)and hepatobiliary diseases(5.35%,0.87%),However,these associations were included in the instructions of allopurinol.Allopurinol was associated with the reproductive system and breast diseases(0.55%),pregnancy,puerperium and perinatal conditions(0.03%),but febuxostat was not found to be involved in the above SOC.Conclusion The inclusion of adverse reactions in the instructions for allopurinol is relatively inadequate compared to buprostat,and the newly discovered involvement of systemic organs and AE can provide a reference for improving allopurinol instructions.This study found that allopurinol and febuxostat allopurinol and febuxostat involved system differences,which can provide reference for clinical individualized treatment.