A real-world disproportionality analysis of ospemifene: data mining of the public version of FDA adverse event reporting system

Ospemifene has been authorized for the treatment of vulvovaginal atrophy (VVA). This study wasto evaluate adverse events (AEs) associated with ospemifene by data mining the US Food and Drug Administration Adverse Event Reporting System (FAERS). The signals of AEs linked to ospemifene were measured using disproportionality analyses, such as the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms. There were 2283 events of ospemifene being the ’primary suspected (PS)’ AE out of the 12,692,824 reports from the FAERS database. Ospemifene-induced AEs hit 25 organ systems. There were 726 severely disproportional preferred terms (PTs) that complied with the four algorithms. The investigation turned up a number of anticipated adverse drug reactions (ADRs), and significant unanticipated ADRs linked to eye and renal problems were found, indicating potential side effects not yet included in the prescription instructions. We detected novel AEs signals for ospemifene, and the results of our investigation were compatible with clinical observations. This suggests that further prospective clinical trials are required to confirm these findings and demonstrate their link. Our findings might be useful supporting data for ospemifene safety research in the future.

奥培米芬（Ospemifene）已被批准用于治疗外阴阴道萎缩（vulvovaginal atrophy, VVA）。本研究旨在通过对美国食品药品监督管理局不良事件报告系统（US Food and Drug Administration Adverse Event Reporting System, FAERS）进行数据挖掘，评估奥培米芬相关不良事件（adverse events, AEs）。研究采用失衡分析方法对奥培米芬相关不良事件信号进行量化分析，所用工具包括报告比值比（reporting odds ratio, ROR）、比例报告比值比（proportional reporting ratio, PRR）、贝叶斯置信传播神经网络（Bayesian confidence propagation neural network, BCPNN）以及多项目伽马泊松收缩器（multi-item gamma Poisson shrinker, MGPS）算法。在FAERS数据库的12692824份报告中，有2283起事件将奥培米芬判定为"主要可疑（primary suspected, PS）"不良事件。奥培米芬相关不良事件涉及25个器官系统。共有726个符合四种算法判定标准的高度失衡首选术语（preferred terms, PTs）。本研究发现了若干已知的药物不良反应（adverse drug reactions, ADRs），同时还检出了与眼部及肾脏问题相关的显著未预期药物不良反应，提示存在尚未纳入药品说明书的潜在不良反应。本研究检出了奥培米芬的新型不良事件信号，研究结果与临床观测数据一致。这表明需开展进一步的前瞻性临床试验以验证本次研究结果并明确其关联性。本研究结果可为未来奥培米芬的安全性研究提供有价值的佐证数据。