基于美国FAERS数据库对替度格鲁肽相关药品不良事件信号的挖掘与分析

Mining and Analysis of Teduglutide-Related Adverse Drug Event Signals Based on the U.S.Food and Drug Administration Adverse Event Reporting System Database

目的:挖掘并分析替度格鲁肽的风险信号,为临床合理用药提供参考。方法:使用OpenVigil 2.1在线数据平台,提取美国食品药品监督管理局不良事件报告系统(FAERS)数据库建库至2023年第4季度的替度格鲁肽相关药品不良事件(ADE)报告,采用比例报告比值(PRR)法和贝叶斯置信区间递进神经网络(BCPNN)法,对替度格鲁肽的ADE信号进行挖掘,根据《国际医学用语词典》(26.1版)对ADE报告进行系统器官分类(SOC)和首选术语(PT)描述。结果:共获得以“替度格鲁肽”为“首要怀疑药物”的ADE报告10955例,涉及女性患者偏多(6207例,占56.66%);45~<65岁患者占比最大(2344例,占21.40%);主要上报国家为美国(8271例,占75.50%)。共挖掘出阳性信号704个、ADE 27112例次,涉及SOC 26种,其中胃肠系统疾病所包含的信号数最多(137个,占19.46%)。按信号强度排序,以造口相关PT(造口部位血栓形成、胃肠造口排便量减少、胃肠造口排便量异常等)为主;按报告频次排序,居前5位的PT为体重降低、血管装置感染、腹泻、恶心、腹痛;新型冠状病毒感染(COVID-19)、外周肿胀等PT未在替度格鲁肽的药品说明书中提及;血管装置感染、造口并发症、装置相关的脓毒症及胃肠造口排便量增加等4个PT的报告频次、PRR信号强度排序均居前50位。结论:替度格鲁肽相关ADE主要分布于胃肠系统疾病,大部分与药品说明书相符。临床需特别注意十二指肠息肉等ADE,建议使用替度格鲁肽的患者在治疗前完善肠镜检查,并在治疗后及时随访。COVID-19和外周肿胀是替度格鲁肽新的潜在ADE,需在未来的治疗中持续关注和进一步验证。

OBJECTIVE:To explore and analyze the risk signal of teduglutide,so as to provide reference for clinical rational drug use.METHODS:The OpenVigil 2.1 online data platform was used to extract teduglutide-related adverse drug event(ADE)reports from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database until the fourth quarter of 2023.The proportional reporting ratio(PRR)method and Bayesian confidence interval progressive neural network(BCPNN)method were used to mine the teduglutide-related ADE signals.According to the International Dictionary of Medical Terms(26.1 Edition),ADE reports were described by Systematic Organ classification(SOC)and preferred term(PT).RESULTS:A total of 10955 ADE reports were obtained,with“teduglutide”as the“primary suspected drugs”,including a higher proportion of female patients(6207 reports,56.66%),with the largest proportion of patients aged from 45 to<65 years(2344 reports,21.40%),mainly reported in the United States(8271 reports,75.50%).A total of 704 positive signals and 27112 ADE cases were detected,involving 26 kinds of SOC,among which the number of signals ranked by gastrointestinal system diseases took the lead(137 signals,19.46%).Sorted by signal intensity,the main focus was on stoma related PT(thrombosis at the stoma site,reduced bowel volume at the gastrointestinal stoma,abnormal bowel volume at the gastrointestinal stoma).Ranked by reporting frequency,the top five PT were body weight loss,vascular device infection,diarrhea,nausea,and abdominal pain.PT such as COVID-19 and peripheral swelling were not mentioned in the drug instructions of teduglutide.Four PT(vascular device infection,stoma complications,device related sepsis,and increased bowel volume at the gastrointestinal stoma)were all ranked on the top 50 in terms of reporting frequency and PRR signal intensity.CONCLUSIONS:Teduglutide-related ADE are mainly in gastrointestinal disorders and most of them are consistent with the drug instructions.Special attention should be paid to ADE such as duodenal polyps in clinical practice.It is recommended that patients who use teduglutide complete colonoscopy before treatment and follow up promptly after treatment.COVID-19 and peripheral swelling are potential ADE of teduglutide,which need to be continuously monitored and further validated in the future treatments.