基于FAERS数据库的真实世界分析: 非唑奈坦和雌二醇不良事件信号挖掘与风险再评价

A real-world analysis based on the FAERS database：mining and risk reassessment of adverse event signals of fezolinetant and estradiol

摘要

目的: 挖掘非唑奈坦和雌二醇药物不良事件 (adverse drug event,ADE) 信号,为女性更年期血管舒缩症状 (vasomotor symptoms,VMS) 合理用药提供临床参考。方法: 从第三方数据平台 OpenVigil 2.1 挖掘美国 FDA 不良事件报告系统 (FDA Adverse Event Reporting System,FAERS) 中非唑奈坦和雌二醇的 ADE信号,采用报告比值比法和比例报告比值比法分析和对比二者的风险信号。结果: 本研究共挖掘 72255 份ADE 报告 (非唑奈坦 1616 例,雌二醇 70639 例) 。经标准化筛选后,非唑奈坦相关 ADE 344 个,33个阳性信号 (绝经期症状、肝脏功能检查值升高和绝经后出血等),涉及11个系统器官分类 (system organ classifica-tion,SOC,包括各类检查、全身性疾病及给药部位各种反应和胃肠系统疾病等) ;雌二醇相关 ADE 3540 个,557 个阳性信号 (子宫肌瘤坏死、睾丸混合型生殖细胞肿瘤和假性性早熟等),覆盖26个 SOC (全身性疾病及给药部位各种反应、产品问题和生殖系统及乳腺疾病等) 。本研究发现了新的潜在风险信号：非唑奈坦包括脑雾、构音障碍、口腔不适及心悸等;雌二醇相关 SOC 则包括良性、恶性及性质不明的肿瘤以及神经、泌尿和胃肠等系统。结论: 非唑奈坦主要 ADE 体现在各种肝功能指标异常和胃肠系统疾病,而雌二醇相关 ADE 则主要表现在产品使用和生殖系统及乳腺疾病方面。临床在治疗患者绝经期 VMS 等症状时,应注意个体化用药,严格监测 ADE。

Abstract

Objective: To detect the adverse drug event (ADE) signals of fezolinetant and estradiol to provide references for rational drug use in treatment of vasomotor symptoms (VMS) in women during menopause. Methods: The ADE signals of fezolinetant and estradiol from the FDA Adverse Event Reporting System (FAERS) database were mined from the third-party data platform OpenVigil 2.1.The reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were adopted to analyze and compare the risk signals of the two drugs. Results: A total of 72255 adverse event reports (1616 cases of fezolinetant and 70639 cases of estradiol) were mined.After standardized screening, 344 cases of fezolinetant-related ADE were detected, and 33 positive signals were detected (menopausal symptoms, elevated liver function test values and postmenopausal bleeding, etc.), involving 11 system organ classification (SOC, all kinds of examinations, systemic diseases and various reactions at the administration site, and gastrointestinal system diseases, etc.).In 3540 estradiol-associated ADE, 557 positive signals were detected (necrosis of uterine fibroids, testicular mixed germ cell tumors and pseudo-precocious puberty, etc.), covering 26 SOC classes (systemic diseases and various reactions at the administration site, product issues, and reproductive system and breast diseases, etc.).This study identified the following new potential risk signals：new ADE related to brain fog, dysarthria, oral discomfort and palpitations were discovered for fezolinetant;the SOC related to the estradiol group included benign, malignant and tumors of unknown nature, as well as those in the nervous, urinary and gastrointestinal systems. Conclusion: The major adverse events of fezolinetant were associated with abnormal liver function indicators and gastrointestinal system diseases, while estradiol related ADE were associated with product use, reproductive system and breast diseases.The treatment of menopausal patients with vasomotor and other symptoms should be individualized and adverse drug reactions should be monitored.

关键词

非唑奈坦 / 雌二醇 / FAERS 数据库 / 药物不良事件 / 回顾性分析

Key words

fezolinetant / estradiol / FAERS database / adverse drug event / retrospective analysis

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基金资助

安徽省教育厅高等学校省级质量工程项目(2024jyxm0769);安徽省高等学校科学研究项目(AHWJ2023BAa20181);安徽省卫生健康科研项目(2024AH050782);安徽医科大学附属医院青年科技人才培养项目(2023cy020)