基于FAERS数据库对拉罗替尼药品不良事件信号的挖掘与分析

Data Mining and Analysis on Adverse Events Signal of Larotrectinib Based on FAERS

目的:挖掘拉罗替尼不良事件(AE)风险信号,为该药的临床安全应用提供参考。方法:检索美国食品药品监督管理局不良事件报告系统(FAERS)数据库,收集2019年第1季度~2022年第4季度以拉罗替尼为首要怀疑药物的AE报告。采用比例失衡测量法中报告比值比(ROR)法挖掘拉罗替尼AE风险信号,报告数≥3、ROR的95%CI下限>1的AE定义为阳性信号,ROR值越大,AE信号越强。采用监管活动医学词典26.0(MedDRA v26.0)的优选术语(PT)和系统器官分类(SOC)对AE进行分类统计,选取阳性信号的PT进行分析。结果:纳入分析的AE报告共479例。采用ROR法进行计算,获得38个阳性信号PT,累及14个SOC,信号较强的SOC为各类神经系统疾病和肝胆系统疾病。药品说明书中未提及的新的不良反应的PT有7个,分别为耐药、肾功能损害、戒断综合征、细胞死亡、胆汁淤积、血胆红素升高、多器官功能不全综合征;累及SOC为5个,分别为全身性疾病及给药部位各种反应、肾脏及泌尿系统疾病、代谢及营养类疾病、肝胆系统疾病、各类检查。结论:神经系统、肝胆系统仍为使用拉罗替尼期间需重点监测的系统器官,拉罗替尼还可能导致耐药、肾功能损伤、胆汁淤积等AE,也需重点关注。

Objective:To explore the risk signals of adverse events(AE)of larotrectinib and provide reference for the safe clinical application of larotrectinib.Methods:The study collected the AE reports involving larotrectinib as the primary suspected drug from 2019 Q1 to 2022 Q4 by searching the Food and Drug Administration Adverse Event Reporting System(FAERS).The reporting odds ratio(ROR)method of proportion imbalance method was used to mine data on the AE risk signal of larotrectinib.A positive signal was defined when the number of reports was≥3 and the lower limit of 95%CI of ROR>1.The larger the ROR value,the stronger the AE signal.AEs were classified according to the preferred term(PT)and system organ class(SOC)classification of the Medical Dictionary for Regulatory Activities 26.0,and PT with positive signal intensity were selected for analysis.Results:A total of 479 AE reports were included in the analysis.The ROR method was used to calculate 38 positive signals,involving 14 SOCs.The SOCs with strong signals were various nervous system diseases and hepatobiliary system diseases.Seven new PT adverse reactions were identified,including drug resistance,renal dysfunction,withdrawal syndrome,cell death,cholestasis,increased blood bilirubin,and multiple organ dysfunction syndrome,which were not mentioned in the instructions.Five SOCs were involved in the analysis,including systemic diseases and various reactions at the drug administration site,kidney and urinary system diseases,metabolic and nutritional diseases,hepatobiliary system diseases,and various examinations.Conclusion:Nervous system and hepatobiliary system should be closely monitored during the use of larotrectinib.Additionally,attention should be given to potential adverse reactions such as drug resistance,renal injury,and cholestasis caused by larotrectinib.