使用FAERS药物警戒数据评估曲普瑞林相关不良事件。

Triptorelin associated adverse events evaluated using FAERS pharmacovigilance data.

作者信息

Jia Wei, Wang Tiezhou

机构信息

Department of Pharmacy, Tonglu branch Hospital, Hangzhou First People's Hospital, No.899 Meilin Road, Tonglu, Hangzhou, 330000, Zhejiang Province, China.

Department of Orthopaedics, Tonglu branch Hospital, Hangzhou First People's Hospital, No.899 Meilin Road, Tonglu, Hangzhou, 330000, Zhejiang Province, China.

出版信息

Sci Rep. 2025 Sep 1;15(1):32042. doi: 10.1038/s41598-025-16734-7.

Abstract

Triptorelin, a gonadotropin-releasing hormone(GnRH) agonist, is approved by the US Food and Drug Administration(FDA) for treating advanced prostate cancer, endometriosis, and central precocious puberty(CPP) in children aged ≥ 2 years. This study aimed to characterize the real-world adverse event(AE) profile associated with triptorelin using data from the FDA Adverse Event Reporting System(FAERS). We conducted a retrospective pharmacovigilance study utilizing FAERS reports from the first quarter of 2004 to the third quarter of 2024 (2004Q1-2024Q3). Disproportionality analysis employing four distinct algorithms (Reporting Odds Ratio [ROR], Proportional Reporting Ratio [PRR], Bayesian Confidence Propagation Neural Network [BCPNN], and Multi-item Gamma Poisson Shrinker [MGPS]) was performed to identify potential statistical signals of triptorelin-associated AEs. Among 18,541,994 eligible FAERS reports, 4018 primary suspect reports involving triptorelin were identified. Disproportionality analysis revealed 102 statistically significant Preferred Terms(PTs). Unexpected statistical signals warranting further investigation included defiant behavior and Alzheimer's dementia. The median time-to-onset (TTO) of AEs was 132 days (interquartile range[IQR] 36-361 days). AE reporting exhibited a bimodal distribution, with the highest proportions occurring within the first month (22.59%) and after more than one year (25.07%) following administration. Distinct statistical signal profiles were observed between genders. Analysis of FAERS data elicited statistical signals for both expected and unexpected AEs associated with triptorelin. These findings highlight potential safety signals, particularly defiant behavior and Alzheimer's dementia, which meet the European Medicines Agency (EMA) 2024 criteria for safety signals requiring further investigation. Continuous pharmacovigilance monitoring is recommended. It is crucial to emphasize that these findings represent statistical associations identified through disproportionality analysis; they require clinical validation and do not establish causality.

摘要

曲普瑞林是一种促性腺激素释放激素(GnRH)激动剂,已获美国食品药品监督管理局(FDA)批准,用于治疗晚期前列腺癌、子宫内膜异位症以及2岁及以上儿童的中枢性性早熟(CPP)。本研究旨在利用FDA不良事件报告系统(FAERS)的数据,描述与曲普瑞林相关的真实世界不良事件(AE)特征。我们进行了一项回顾性药物警戒研究,使用了2004年第一季度至2024年第三季度(2004Q1 - 2024Q3)的FAERS报告。采用四种不同算法(报告比值比[ROR]、比例报告比值比[PRR]、贝叶斯置信传播神经网络[BCPNN]和多项目伽马泊松收缩器[MGPS])进行不成比例分析,以识别曲普瑞林相关不良事件的潜在统计信号。在18541994份符合条件的FAERS报告中,识别出4018份涉及曲普瑞林的主要可疑报告。不成比例分析揭示了102个具有统计学意义的首选术语(PTs)。需要进一步调查的意外统计信号包括挑衅行为和阿尔茨海默病性痴呆。不良事件的中位发病时间(TTO)为132天(四分位间距[IQR] 36 - 361天)。不良事件报告呈现双峰分布,给药后第一个月内发生率最高(22.59%),一年以上后发生率次之(25.07%)。不同性别之间观察到不同的统计信号特征。对FAERS数据的分析得出了与曲普瑞林相关的预期和意外不良事件的统计信号。这些发现突出了潜在的安全信号,特别是挑衅行为和阿尔茨海默病性痴呆,它们符合欧洲药品管理局(EMA)2024年关于需要进一步调查的安全信号的标准。建议持续进行药物警戒监测。必须强调的是,这些发现是通过不成比例分析确定的统计关联;它们需要临床验证,且未确立因果关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110e/12402341/de939f03f393/41598_2025_16734_Fig1_HTML.jpg

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