Liu Fengfen, Su Huaiyu, Wei Wei
Department of Pharmacy, People's Hospital of Deyang City, Deyang, China.
Department of Pharmacy, People's Hospital of Zhongjiang County, Deyang, China.
Sci Rep. 2025 Mar 17;15(1):9218. doi: 10.1038/s41598-025-92741-y.
The FDA has granted approval for the use of selumetinib in the treatment of pediatric patients who are at least 2 years old and have neurofibromatosis type 1 (NF1) with symptomatic, inoperable plexiform neurofibromas (PN). Nevertheless, the safety of selumetinib over an extended period of time in sizable cohorts remains uncertain. The objective of the present study was to assess the adverse events (AEs) associated with selumetinib by analyzing data from the US food and drug administration adverse event reporting system (FAERS). The FAERS database was retrospectively queried to extract reports associated with selumetinib from the third quarter of 2020 to the first quarter of 2024. To identify and evaluate potential AEs in patients receiving selumetinib, various 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) were employed. A total of 546 reports of selumetinib as the "primary suspected (PS)" and 1437 cases of selumetinib-induced AEs were identified. 42 AE signals were detected at the preferred term (PT) level after complying with four algorithms simultaneously. Commonly significant signals for cardiotoxicity, ocular toxicity, skin toxicity, and increased creatine phosphokinase have been observed. Additionally, previously reported AE signals such as proteinuria were detected. Most AEs related to selumetinib occur within the first month after the initiation of therapy. Our study improves the comprehension of selumetinib's safety profile by offering a thorough analysis of the adverse events (AEs) recorded post-marketing. These findings highlight the necessity of ongoing surveillance to detect and assess any adverse events linked to selumetinib.
美国食品药品监督管理局(FDA)已批准使用司美替尼治疗至少2岁、患有1型神经纤维瘤病(NF1)且有症状的、无法手术的丛状神经纤维瘤(PN)的儿科患者。然而,司美替尼在大量队列中的长期安全性仍不确定。本研究的目的是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,评估与司美替尼相关的不良事件(AE)。对FAERS数据库进行回顾性查询,以提取2020年第三季度至2024年第一季度与司美替尼相关的报告。为了识别和评估接受司美替尼治疗的患者中的潜在AE,采用了各种不成比例分析方法,如报告比值比(ROR)、比例报告比(PRR)、贝叶斯置信传播神经网络(BCPNN)和多项目伽马泊松收缩器(MGPS)。共识别出546份将司美替尼列为“主要疑似药物(PS)”的报告以及1437例司美替尼引起的AE病例。在同时符合四种算法后,在首选术语(PT)级别检测到42个AE信号。已观察到心脏毒性、眼毒性、皮肤毒性和肌酸磷酸激酶升高的常见显著信号。此外,还检测到了先前报告的如蛋白尿等AE信号。大多数与司美替尼相关的AE发生在治疗开始后的第一个月内。我们的研究通过对上市后记录的不良事件(AE)进行全面分析,提高了对司美替尼安全性概况的理解。这些发现凸显了持续监测以检测和评估与司美替尼相关的任何不良事件的必要性。