基于FAERS数据库的芳香化酶抑制剂不良事件信号挖掘研究

Data-mining and Analysis of Adverse Events Signals for Aromatase Inhibitors Based on FAERS Database

关键词:  美国FDA不良事件报告系统(FAERS)  芳香化酶抑制剂  信号挖掘  不良事件  比例失衡法

Key words:  FAERS  aromatase inhibitor  signals data-mining  adverse drug events  measures of disproportionality

摘要:

目的 对芳香化酶抑制剂(aromatase inhibitors，AIs)的不良事件(adverse drug event，ADE)信号进行挖掘分析，为临床安全用药提供参考。方法 从美国FDA不良事件报告系统提取2015年第1季度—2021年第2季度共26个季度的与AIs相关的ADE报告，数据规范化后，利用报告比值比法和比例报告比值法对ADE报告进行数据筛选与分析。结果 共获得以AIs为首要怀疑药物的ADE报告共16501份，筛选后得到ADE信号1150个(依西美坦209个，来曲唑377个，阿那曲唑564个)，累及23个系统，主要涉及各种肌肉骨骼及结缔组织疾病和全身性疾病及给药部位各种反应等。报告数前50位的ADE中未在说明书中出现的信号有47个(依西美坦15个，来曲唑11个，阿那曲唑21个)，新信号主要集中在血液、心血管和呼吸系统。结论 本研究挖掘出的常见ADE信号和其累及系统与说明书一致，但3种AIs的ADE具有差异性且发现新信号，可为临床合理用药提供一定的参考。

Abstract:

OBJECTIVE To provide reference for safe and rational drug use in clinic by mining and analysis of adverse drug event(ADE) signals of aromatase inhibitors(AIs). METHODS Data of ADE reports related to AIs in the first quarter of 2015 to second quarter of 2021 included 26 quarterlies were collected from US FDA adverse event reporting system. After data standardization, the reporting odd ratio method and the proportional reporting ratio method were used for ADE signal screening and analysis. RESULTS A total of 16 501 ADE reports with AIs as the primary suspected drug were extracted. The 1 150 effective ADE signals(exemestane 209, letrozole 377 and anastrozole 564) were obtained after screening, involving 23 systems organ classes and mainly focusing on various musculoskeletal and connective tissue diseases, systemic diseases and various reactions of drug administration sites and so on. In the sequence of top 50, there were 47 signals that did not appear in the instruction, including exemestane 15, letrozole 11 and anastrozole 21, and the new signals were concentrated in the blood, cardiovascular and respiratory systems. CONCLUSION The common ADE signals and involved systems obtained in study are consistent with the instructions. However, ADE of the three AIs are different and new signals are found, which can provide certain reference for clinical rational drug use.