Liu Hua, Fan Dandan, Tao Hong, Shen Zhu, Yao Kun
Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu Province, China.
Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Cerebellum. 2025 Jun 18;24(4):119. doi: 10.1007/s12311-025-01873-4.
Omaveloxolone, the first approved therapeutic agent for Friedreich ataxia (FRDA), currently has limited real-world safety data available. This study aims to evaluate post-marketing adverse events (AEs) associated with its clinical use by analyzing data from the FDA Adverse Event Reporting System (FAERS). We collected all adverse reaction reports associated with omaveloxolone from the first quarter of 2023 (Q1 2023) to the fourth quarter of 2024 (Q4 2024) in the FAERS database and performed signal detection using four distinct pharmacovigilance methods: the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). A total of 9,326,057 AE reports were collected, among which 820 reports were associated with omaveloxolone. All AEs were categorized into 25 System Organ Classes (SOCs) and 67 positive Preferred Terms (PTs). Investigations represented the most frequently reported SOC, followed by gastrointestinal disorders and general disorders and administration site conditions. Hepatic enzyme increased emerged as the most prominent adverse event, demonstrating both high reporting frequency and strong signal intensity, primarily manifesting as elevated ALT and AST levels. Other commonly reported AEs included fatigue, nausea, headache, and blood cholesterol increased. The study also identified several novel potential AEs, such as urinary tract infection, diabetes mellitus, urine odour abnormal, atrial flutter, and urosepsis. Although some of these AEs were reported in relatively low frequencies, their clinical severity and elevated signal strengths suggest that omaveloxolone may potentially affect patients' urinary and endocrine systems, warranting particular attention during clinical administration. In conclusion, while omaveloxolone demonstrates multifaceted benefits in improving neurological function in patients with FRDA, its clinical application necessitates comprehensive evaluation of potential risks, and the development of safe and rational therapeutic strategies is crucial for optimizing treatment outcomes.
奥马维洛酮是首个获批用于治疗弗里德赖希共济失调（FRDA）的治疗药物，目前可获得的真实世界安全性数据有限。本研究旨在通过分析美国食品药品监督管理局不良事件报告系统（FAERS）的数据，评估其临床使用相关的上市后不良事件（AE）。我们收集了FAERS数据库中2023年第一季度（2023年Q1）至2024年第四季度（2024年Q4）与奥马维洛酮相关的所有不良反应报告，并使用四种不同的药物警戒方法进行信号检测：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）和经验贝叶斯几何均值（EBGM）。共收集到9326057份AE报告，其中820份与奥马维洛酮相关。所有AE被分为25个系统器官类别（SOC）和67个阳性首选术语（PT）。检查是报告最频繁的SOC，其次是胃肠道疾病以及全身性疾病和给药部位情况。肝酶升高成为最突出的不良事件，显示出高报告频率和强信号强度，主要表现为ALT和AST水平升高。其他常见报告的AE包括疲劳、恶心、头痛和血胆固醇升高。该研究还识别出几种新的潜在AE，如尿路感染、糖尿病、尿味异常、心房扑动和尿脓毒症。尽管其中一些AE报告频率相对较低，但其临床严重程度和升高的信号强度表明奥马维洛酮可能潜在影响患者的泌尿系统和内分泌系统，在临床给药期间需要特别关注。总之，虽然奥马维洛酮在改善FRDA患者神经功能方面显示出多方面益处，但其临床应用需要对潜在风险进行全面评估，制定安全合理的治疗策略对于优化治疗结果至关重要。
