Zhang Ying, Ran Li, Liang Yongchao, Zhang Yanqiu, An Zhuoling
Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Front Pharmacol. 2023 Jul 24;14:1194545. doi: 10.3389/fphar.2023.1194545. eCollection 2023.
Cholangiocarcinoma (CCA) is a highly lethal and aggressive epithelial tumor of the hepatobiliary system. A poor prognosis, propensity for relapse, low chance of cure and survival are some of its hallmarks. Pemigatinib, the first targeted treatment for CCA in the United States, has been demonstrated to have a significant response rate and encouraging survival data in early-phase trials. The adverse events (AEs) of pemigatinib must also be determined. To understand more deeply the safety of pemigatinib in the real world through data-mining of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Disproportionality analysis was employed in a retrospective pharmacovigilance investigation to identify the AEs linked to pemigatinib use as signals. Data were collected between 1 January 2020 to 30 June 2022. Four data-mining methods (proportional reporting odds ratio; proportional reporting ratio; Bayesian confidence propagation neural networks of information components; empirical Bayes geometric means) were used to calculate disproportionality. A total of 203 cases using pemigatinib as the prime-suspect medication were found in our search, which involved 99 preferred terms (PTs). Thirteen signals of pemigatinib-induced AEs in seven System Organ Classes were detected after confirming the four algorithms simultaneously. Nephrolithiasis was an unexpected significant AE not listed on the drug label found in our data-mining. Comparison of the differences between pemigatinib and platinum drugs in terms of 33 PTs revealed that 13 PTs also met the criteria of the four algorithms. Ten of these PTs were identical to those compared with all other drugs, in which (excluding a reduction in phosphorus in blood) other PT signal values were higher than those of all other drugs tested. However, comparison of the differences between pemigatinib and infigratinib in terms of the 33 PTs revealed no significant signals in each algorithm method. Some significant signals were detected between pemigatinib use and AEs. PTs with apparently strong signals and PTs not mentioned in the label should be taken seriously.
胆管癌（CCA）是一种高度致命且侵袭性强的肝胆系统上皮肿瘤。预后差、易复发、治愈和生存几率低是其一些特征。培米替尼是美国首个用于CCA的靶向治疗药物，在早期试验中已证明具有显著的缓解率和令人鼓舞的生存数据。培米替尼的不良事件（AE）也必须确定。通过对美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）进行数据挖掘，更深入地了解培米替尼在现实世界中的安全性。在一项回顾性药物警戒调查中采用不成比例分析，以确定与使用培米替尼相关的AE作为信号。收集了2020年1月1日至2022年6月30日期间的数据。使用四种数据挖掘方法（比例报告比值比；比例报告率；信息成分的贝叶斯置信传播神经网络；经验贝叶斯几何均值）来计算不成比例性。在我们的搜索中总共发现了203例将培米替尼作为主要怀疑药物的病例，涉及99个首选术语（PT）。在同时确认这四种算法后，检测到培米替尼诱导的AE在七个系统器官类别中的13个信号。肾结石是我们数据挖掘中在药物标签上未列出的意外显著AE。对培米替尼和铂类药物在33个PT方面的差异进行比较发现，其中13个PT也符合这四种算法的标准。这些PT中有10个与与所有其他药物比较时的PT相同，其中（不包括血液中磷的降低）其他PT信号值高于所有其他测试药物。然而，对培米替尼和英菲格拉替尼在33个PT方面的差异进行比较发现，在每种算法方法中均未发现显著信号。在使用培米替尼与AE之间检测到一些显著信号。具有明显强信号的PT和标签中未提及的PT应予以重视。
