基于美国FDA公共数据开放项目平台的利马前列素不良事件风险信号挖掘

Signal mining of adverse event risk of limaprost based on US FDA Public Data Open Project platform

目的挖掘利马前列素不良事件(AE)的风险信号,为临床安全使用该药提供参考。方法检索美国FDA公共数据开放项目(OpenFDA)平台,收集2004年1月1日至2023年10月1日收到的利马前列素AE报告,根据《国际医学用语词典》25.1版系统器官分类(SOC)和首选术语(PT)对AE进行分类和标准化编码,采用报告比值比(ROR)法挖掘利马前列素的风险信号,将AE报告数≥3、ROR≥2且其95%置信区间(CI)下限>1的PT定义为风险信号,对风险信号进行描述性分析。结果收集到以利马前列素为首要怀疑药物的AE报告1618例,挖掘出69个风险信号,涉及17个SOC。10个风险信号为说明书已记载的不良反应,包括肝功能异常、红细胞计数下降、药疹、血压降低、肝脏疾病、血小板计数降低、贫血、血红蛋白降低、发热和食欲减退。59个风险信号为说明书未记载AE,信号强度居前10位者为硬肿症、肿瘤出血、脑利尿钠肽升高、抗利尿激素分泌失调、显微镜下结肠炎、大肠穿孔、急性心力衰竭、抑郁症状、慢性心力衰竭、肺泡出血;报告数>10的信号为抗利尿激素分泌失调、间质性肺疾病、肾损伤、心力衰竭、感染性肺炎、跌倒等。结论除说明书记载的不良反应外,利马前列素还可能引起肿瘤出血、脑利尿钠肽升高和抗利尿激素分泌失调等说明书未记载且预后不良的严重不良事件。

Objective To mine the risk signals of adverse events of limaprost and provide reference for safe use of the drug.Methods US FDA Public Data Open Project(OpenFDA)platform was searched,and the adverse event(AE)reports on limaprost from January 1,2004 to October 1,2023 were collected.AEs were classified and standardized according to the system organ class(SOC)and preferred terms(PT)of Medical Dictionary for Regulatory Activities version 25.1.The reporting odds ratio(ROR)method was used to mine the risk signal of limaprost.An AE with reports≥3,ROR≥2 and the lower limit of the 95%confidence interval(CI)>1 was defined as a risk signal,which was analyzed descriptively.Results A total of 1618 AE reports with limaprost as the primary suspect drug were collected,69 risk signals were identified,involving 17 SOCs.Of the 69 PTs,10 were recorded in the drug instructions including hepatic function abnormal,red blood cell count decreased,drug eruption,blood pressure decreased,liver disorder,platelet count decreased,anaemia,haemoglobin decreased,pyrexia,and decreased appetite.The other 59 risk signals were not recorded in the drug instructions.The top 10 PTs in signal intensity were scleroderma,tumour haemorrhage,brain natriuretic peptide increased,inappropriate antidiuretic hormone secretion,colitis microscopic,large intestine perforation,cardiac failure acute,depressive symptom,cardiac failure chronic,pulmonary alveolar haemorrhage.The risk signals with more than 10 reports were inappropriate antidiuretic hormone secretion,interstitial lung disease,renal impairment,cardiac failure,pneumonia,fall,etc.Conclusion In addition to the AEs recorded in the instructions,limaprost may also cause serious adverse reactions such as tumour haemorrhage,brain natriuretic peptide increased,and inappropriate antidiuretic hormone secretion,which are not recorded in the instructions and have a poor prognosis.