基于OpenFDA对3种BTK抑制剂的不良事件信号分析

Adverse Event Signal Analysis of Three BTK Inhibitors Based on OpenFDA

关键词:  BTK抑制剂  OpenFDA  不良反应信号挖掘  报告比值比法  比例报告比值法

Key words:  BTK inhibitors  OpenFDA  adverse reaction signal mining  reporting odds ratio  proportional reporting ratio

摘要:

目的 通过对伊布替尼、阿卡替尼和泽布替尼3种布鲁顿酪氨酸激酶(Bruton’s tyrosine kinase，BTK)抑制剂不良事件风险信号挖掘分析，为临床安全用药提供参考。方法 基于美国食品药品监督管理局公共数据开放项目(OpenFDA)，对3种BTK抑制剂2004年1月1日—2021年9月30日的不良事件上报数据进行检索。结果 FDA收到的伊布替尼、阿卡替尼和泽布替尼不良事件各为49 006，2 056，246份。采用比例失衡法检测，具有统计学意义的不良事件信号共计769个，主要集中于感染及侵染类、血液及淋巴系统、心脏器官疾病、皮肤及皮下组织类、血管与淋巴管类等，也挖掘到一些新的不良事件，如败血症、肺出血、指甲疾病、脆甲症、味觉障碍等。伊布替尼不良事件风险信号最多，三者各不良事件风险信号相关性有所区别。结论 利用OpenFDA数据库对3种BTK抑制剂多维度挖掘分析，提示临床医师在临床使用过程中警惕药物不良事件风险，及时对症处理，促进合理用药。

Abstract:

OBJECTIVE To provide reference for clinical safe drug use by mining and analyzing the risk signals of adverse events of three Bruton’s tyrosine kinase(BKT) inhibitors, ibrutinib, acalabrutinib and zanubrutinib. METHODS Based on the Public Data Open Project of the US Food and Drug Administration(OpenFDA), adverse event reporting data for three BTK inhibitors from January 1, 2004 to September 30, 2021 were retrieved. RESULTS According to the FDA, 49 006, 2 056 and 246 adverse events had been reported in relation to ibrutinib, acalabrutinib, and zanubrutinib, respectively. Using the proportional imbalance method for detection, there were a total of 769 adverse event signals with statistical significance, which were mainly focused on infection, blood and lymphatic system, heart diseases, skin and subcutaneous tissue, vascular and lymphatic vessel vessels, etc. In addition, new adverse events were observed, such as sepsis, pulmonary hemorrhage, nail disorder, brittle nails, taste disorder, etc. Compared to acalabrutinib and zanubrutinib, ibrutinib had the most adverse event risk signals, and the correlations of adverse event risk signals among them were diverse. CONCLUSION By conducting a multi-dimensional mining analysis of the three BTK inhibitors using the OpenFDA database, the study prompts clinical physicians to be alert to the risk of adverse drug events during clinical use, timely diagnose and treat corresponding symptoms, so as to promote rational drug use.