与CDK4/6抑制剂相关的感染：FDA不良事件报告系统数据库的药物警戒分析

Infection associated with CDK4/6 inhibitors: a pharmacovigilance analysis of the FDA adverse event reporting system database

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Frontiers in Pharmacology

影响因子:4.8

分区:医学3区 / 药学3区

发表日期:2024

作者: Jinhua Chen, Linlin Tang, Wenping Song, Cuicui Sun, Wenzhou Zhang

DOI: 10.3389/fphar.2024.1371346

摘要

环素依赖激酶4/6（CDK4/6）抑制剂是激素受体阳性/人类表皮生长因子受体2阴性乳腺癌的一线治疗药物。随着其临床应用的增加，近年来关于CDK4/6抑制剂相关感染不良事件（AEs）的报道日益增多。本研究旨在基于美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）数据库的真实世界数据，分析与CDK4/6抑制剂（帕博昔尼、瑞博昔尼和阿贝昔尼）相关的感染事件的发生情况。数据来源于2015年第一季度至2022年第三季度的FAERS数据库。分析患者的主要疑似感染相关AEs的临床特征，采用不成比例性分析探讨AEs与药物的潜在关联。影响因素通过Pearson卡方检验评估。感染相关AEs中，瑞博昔尼的报告占比8.58%，高于帕博昔尼（2.72%）和阿贝昔尼（1.24%）。瑞博昔尼相关的严重不良事件比例为67.65%，高于帕博昔尼的30%和阿贝昔尼的48.08%。性别和年龄与结局严重程度无显著相关性。不成比例性分析显示，帕博昔尼、瑞博昔尼和阿贝昔尼均检测到不同的感染相关优选术语（preferred terms）。综上，基于FAERS数据库的真实世界数据，感染相关AEs与三种CDK4/6抑制剂高度相关，特别是帕博昔尼和瑞博昔尼，但仍需进一步的因果关系评估。

Abstract

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are first-line treatments for hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. With their increasing clinical use, infection-related adverse events (AEs) associated with CDK4/6 inhibitors have been widely reported in recent years. This study aimed to analyze the occurrence of infections associated with the CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) based on the real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.Data were extracted from the FAERS database between 2015Q1 and 2022Q3. The clinical characteristics of patients with primary suspected infection-related AEs were analyzed. A disproportionality analysis was performed to investigate the potential association between AEs and CDK4/6 inhibitors. The influencing factors were evaluated using Pearson's chi-square test.Reports of infection-related AEs associated with ribociclib accounted for 8.58% of the total reports of AEs associated with ribociclib, followed by palbociclib (2.72%) and abemaciclib (1.24%). Ribociclib (67.65%) was associated with more serious outcome events than palbociclib (30%) or abemaciclib (48.08%). The sex and age were not associated with outcome severity. Disproportionality analysis showed that fourteen, sixteen and two infection-related preferred terms were detected for palbociclib, ribociclib and abemaciclib, respectively.Infection-related AEs were highly associated with three CDK4/6 inhibitors, especially palbociclib and ribociclib, based on the real-world data from the FAERS database. However, further causality assessment is required.