Zhao Jiawei, Tao Yong
Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Front Pharmacol. 2024 Aug 9;15:1393940. doi: 10.3389/fphar.2024.1393940. eCollection 2024.
Teprotumumab, an IGF-1R monoclonal antibody, has shown significant efficacy in treating thyroid eye disease (TED). However, since teprotumumab was launched in 2020 and first approved in the United States, there were limited reports of post-marketing adverse events (AEs). In this study, we aimed to mine and analyze the AEs signals with teprotumumab on the basis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to provide instructions in clinical practice concerning adverse reactions and assistance in drug development and import/export into other countries.
All AE reports were obtained from the FAERS database from the first quarter of 2020 to the fourth quarter of 2023. To comprehensively analyze the AEs, we applied four disproportionality analysis algorithms, including 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.
A total of 687 reports from 200 patients related to administration of teprotumumab were obtained, and 78% of the cases was female. Signal detection of teprotumumab at the system organ class (SOC) level included gastrointestinal disorders, ear and labyrinth disorders, general disorders and administration site conditions, nervous system disorders, and musculoskeletal and connective tissue disorders. AEs that ranked top five at the preferred terms (PTs) level were muscle spasms, fatigue, tinnitus, headache, and deafness. The median time to those AEs onsets was 48 days (interquartile range 19.0-92.0 days) after administering drugs. Additionally, our results indicated the AEs in reproductive system and breast disorders because the prevalence of TED was more common in women.
This study identified many AEs associated with teprotumumab and unveiled potential new AE signals. These results can provide valuable evidence for further clinical application of teprotumumab and are important in enhancing clinical medication safety.
替普罗珠单抗是一种胰岛素样生长因子-1受体（IGF-1R）单克隆抗体，已显示出在治疗甲状腺眼病（TED）方面具有显著疗效。然而，自替普罗珠单抗于2020年上市并首次在美国获批以来，上市后不良事件（AE）的报告有限。在本研究中，我们旨在基于美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）挖掘和分析替普罗珠单抗的AE信号，为临床实践中有关不良反应提供指导，并为药物研发及进出口到其他国家提供帮助。
所有AE报告均从2020年第一季度至2023年第四季度的FAERS数据库中获取。为全面分析AE，我们应用了四种不成比例分析算法，包括报告比值比（ROR）、比例报告比（PRR）、贝叶斯置信传播神经网络（BCPNN）和多项伽马泊松收缩器（MGPS）算法。
共获得200例患者的687份与替普罗珠单抗给药相关的报告，其中78%的病例为女性。在系统器官分类（SOC）水平上替普罗珠单抗的信号检测包括胃肠道疾病、耳和迷路疾病、全身性疾病及给药部位状况、神经系统疾病以及肌肉骨骼和结缔组织疾病。在首选术语（PT）水平上排名前五的AE为肌肉痉挛、疲劳、耳鸣、头痛和耳聋。这些AE发生的中位时间为给药后48天（四分位间距19.0 - 92.0天）。此外，由于TED在女性中更为常见，我们的结果还表明了生殖系统和乳腺疾病方面的AE。
本研究确定了许多与替普罗珠单抗相关的AE，并揭示了潜在的新AE信号。这些结果可为替普罗珠单抗的进一步临床应用提供有价值的证据，对于提高临床用药安全性具有重要意义。
