He Qining, Jiang Mengting, Wang Yuchen, Zheng Tao
Department of Abdominal Acute Care Surgery, General Surgery Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Br J Clin Pharmacol. 2025 Dec;91(12):3445-3460. doi: 10.1002/bcp.70186. Epub 2025 Aug 7.
Obeticholic acid (OCA) is a farnesoid X nuclear receptor agonist that was approved by the Food and Drug Administration in 2016 for the treatment of primary biliary cholangitis. The aim of this study was to investigate the adverse events (AEs) associated with OCA.
We extracted data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the second quarter of 2016 to the first quarter of 2025. Disproportionality analyses were conducted to assess risk signals of AEs associated with OCA through 4 algorithms, encompassing reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network and empirical Bayesian geometric mean.
Out of 14 859 866 reports from the FAERS database, 6177 reports with OCA as principal suspect AEs were identified. Across 27 organ systems, we identified 187 significant disproportionate preferred terms, which mainly concentrated on gastrointestinal, hepatobiliary, skin and subcutaneous tissue disorders. We also observed unlisted adverse reactions, such as oesophageal varices (ROR 58.39 [95% confidence interval 43.67-78.08]) and hepatic fibrosis (ROR 74.95 [95% confidence interval 58.59-95.88]). Most AEs occurred within 30 days or after 1 year of medication, and were more frequent in female patients.
This real-world study identified OCA-associated AEs, especially some not recorded in the drug insert, and revealed delayed AEs beyond 1 year. These findings highlight the importance of active monitoring for patient medication safety, and we recommend that the monitoring duration be no less than 1 year.
奥贝胆酸（OCA）是一种法尼醇X核受体激动剂，于2016年获美国食品药品监督管理局批准用于治疗原发性胆汁性胆管炎。本研究旨在调查与奥贝胆酸相关的不良事件（AE）。
我们从美国食品药品监督管理局不良事件报告系统（FAERS）数据库中提取了2016年第二季度至2025年第一季度的数据。通过4种算法进行比例失衡分析，以评估与奥贝胆酸相关的不良事件的风险信号，这4种算法包括报告比值比（ROR）、比例报告比、贝叶斯置信传播神经网络和经验贝叶斯几何均值。
在FAERS数据库的14859866份报告中，确定了6177份以奥贝胆酸为主要可疑不良事件的报告。在27个器官系统中，我们确定了187个显著不成比例的首选术语，主要集中在胃肠道、肝胆、皮肤和皮下组织疾病。我们还观察到未列出的不良反应，如食管静脉曲张（ROR 58.39 [95%置信区间43.67 - 78.08]）和肝纤维化（ROR 74.95 [95%置信区间58.59 - 95.88]）。大多数不良事件发生在用药后30天内或1年后，且在女性患者中更常见。
这项真实世界研究确定了与奥贝胆酸相关的不良事件，特别是一些未记录在药品说明书中的事件，并揭示了超过1年的延迟不良事件。这些发现凸显了对患者用药安全进行主动监测的重要性，我们建议监测持续时间不少于1年。
