Safety profiles of IDH inhibitors: a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database

IF 3.4 Q2 PHARMACOLOGY & PHARMACY
Ximu Sun, Han Zhou, Yanming Li, Yanhui Luo, Qixiang Guo, Yixin Sun, Chenguang Jia, Bin Wang, Maoquan Qin, Peng Guo
{"title":"Safety profiles of IDH inhibitors: a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database","authors":"Ximu Sun,&nbsp;Han Zhou,&nbsp;Yanming Li,&nbsp;Yanhui Luo,&nbsp;Qixiang Guo,&nbsp;Yixin Sun,&nbsp;Chenguang Jia,&nbsp;Bin Wang,&nbsp;Maoquan Qin,&nbsp;Peng Guo","doi":"10.1186/s43094-025-00769-8","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>With the increased use of isocitrate dehydrogenase (IDH) inhibitors in acute myeloid leukemia (AML) and cholangiocarcinoma, the toxicity of these drugs is a growing concern. This study aimed to evaluate the adverse events (AEs) of IDH inhibitors based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database.</p><h3>Methods</h3><p>AE reports for IDH inhibitors (enasidenib, ivosidenib, and olutasidenib) were collected and analyzed from the time of launch through the first quarter of 2024. Only IDH inhibitors reported as the target drug and coded as the primary suspect (PS) were included in the analysis. AEs were standardized and classified according to the preferred term (PT) and system organ classification (SOC) in the Medical Dictionary for Regulatory Activities (MedDRA) version 26.0. Disproportionality analyses including the reporting odds ratio and the Bayesian confidence propagation neural network were performed in data mining to assess IDH inhibitor-relatedAEs. Differentiation syndrome was the AE of special interest.</p><h3>Results</h3><p>The reports number of enasidenib, ivosidenib, and olutasidenib was 11 616 357, 10 067 250, and 2 563 464, respectively. A total of 80 enasidenib-related signals involving 15 SOCs, 78 ivosidenib-related signals involving 17 SOCs, and 7 olutasidenib-related signals involving 4 SOCs were obtained. The most signals reported were “blood and lymphatic system disorders,” “infections and infestations,” and “nervous system disorders” in enasidenib. For signals of ivosidenib, the most frequently reported were “gastrointestinal disorders,” “general disorders and administration site conditions,” and “injury, poisoning and procedural complications.” Ivosidenib was the only IDH inhibitor with signals in “cardiac disorders.” Differentiation syndrome events were reported in 89, 40, and 2 cases for enasidenib, ivosidenib, and olutasidenib, respectively. The median time to onset was 26–31 days for ivosidenib and enasidenib. AML was the most common indication in the differentiation syndrome reports.</p><h3>Conclusions</h3><p>Our study identifies potential AE signals associated with IDH inhibitors and provides a broader understanding of the safety. The safety profiles highlight the need for long-term safety monitoring of IDH inhibitor recipients. Promptly monitoring and intervention in specific organ systems depending on the type of IDH inhibitor may improve the overall survival or enhance the quality of life. In the future, it will be necessary to validate our findings in prospective large-scale studies and to investigate the underlying mechanisms.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"11 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-025-00769-8","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Future Journal of Pharmaceutical Sciences","FirstCategoryId":"1085","ListUrlMain":"https://link.springer.com/article/10.1186/s43094-025-00769-8","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Background

With the increased use of isocitrate dehydrogenase (IDH) inhibitors in acute myeloid leukemia (AML) and cholangiocarcinoma, the toxicity of these drugs is a growing concern. This study aimed to evaluate the adverse events (AEs) of IDH inhibitors based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods

AE reports for IDH inhibitors (enasidenib, ivosidenib, and olutasidenib) were collected and analyzed from the time of launch through the first quarter of 2024. Only IDH inhibitors reported as the target drug and coded as the primary suspect (PS) were included in the analysis. AEs were standardized and classified according to the preferred term (PT) and system organ classification (SOC) in the Medical Dictionary for Regulatory Activities (MedDRA) version 26.0. Disproportionality analyses including the reporting odds ratio and the Bayesian confidence propagation neural network were performed in data mining to assess IDH inhibitor-relatedAEs. Differentiation syndrome was the AE of special interest.

Results

The reports number of enasidenib, ivosidenib, and olutasidenib was 11 616 357, 10 067 250, and 2 563 464, respectively. A total of 80 enasidenib-related signals involving 15 SOCs, 78 ivosidenib-related signals involving 17 SOCs, and 7 olutasidenib-related signals involving 4 SOCs were obtained. The most signals reported were “blood and lymphatic system disorders,” “infections and infestations,” and “nervous system disorders” in enasidenib. For signals of ivosidenib, the most frequently reported were “gastrointestinal disorders,” “general disorders and administration site conditions,” and “injury, poisoning and procedural complications.” Ivosidenib was the only IDH inhibitor with signals in “cardiac disorders.” Differentiation syndrome events were reported in 89, 40, and 2 cases for enasidenib, ivosidenib, and olutasidenib, respectively. The median time to onset was 26–31 days for ivosidenib and enasidenib. AML was the most common indication in the differentiation syndrome reports.

Conclusions

Our study identifies potential AE signals associated with IDH inhibitors and provides a broader understanding of the safety. The safety profiles highlight the need for long-term safety monitoring of IDH inhibitor recipients. Promptly monitoring and intervention in specific organ systems depending on the type of IDH inhibitor may improve the overall survival or enhance the quality of life. In the future, it will be necessary to validate our findings in prospective large-scale studies and to investigate the underlying mechanisms.

IDH抑制剂的安全性概况:FDA不良事件报告系统(FAERS)数据库的药物警戒分析
背景:随着异柠檬酸脱氢酶(IDH)抑制剂在急性髓性白血病(AML)和胆管癌中的应用增加,这些药物的毒性越来越受到关注。本研究旨在基于美国食品和药物管理局不良事件报告系统(FAERS)数据库评估IDH抑制剂的不良事件(ae)。方法收集IDH抑制剂(enasidenib、ivosidenib和olutasidenib)从上市到2024年第一季度的报告并进行分析。只有IDH抑制剂被报道为靶药物并被编码为主要嫌疑人(PS)被纳入分析。根据《药物调节活动医学词典》(MedDRA) 26.0版的首选术语(PT)和系统器官分类(SOC)对ae进行标准化分类。在数据挖掘中进行歧化分析,包括报告优势比和贝叶斯置信传播神经网络,以评估IDH抑制剂相关ae。辨证是特别关注的AE。结果enasidenib、ivosidenib、olutasidenib报告数分别为11 616 357、10 067 250、2 563 464。共获得80个enasidenib相关信号,涉及15个soc, 78个ivosidenib相关信号,涉及17个soc, 7个olutasidenib相关信号,涉及4个soc。在enasidenib中,报告最多的信号是“血液和淋巴系统紊乱”、“感染和感染”和“神经系统紊乱”。对于伊沃sidenib的信号,最常见的报道是“胃肠道疾病”、“一般疾病和给药部位情况”和“损伤、中毒和手术并发症”。Ivosidenib是唯一具有“心脏疾病”信号的IDH抑制剂。enasidenib、ivosidenib和olutasidenib分别报告了89例、40例和2例分化证事件。ivosidenib和enasidenib的中位发病时间为26-31天。AML是辨证报告中最常见的适应症。结论sour研究发现了与IDH抑制剂相关的潜在AE信号,并为其安全性提供了更广泛的理解。安全性概况强调需要对IDH抑制剂受体进行长期安全监测。根据IDH抑制剂的类型,及时监测和干预特定的器官系统可能会改善总生存率或提高生活质量。在未来,有必要在前瞻性的大规模研究中验证我们的发现并调查潜在的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
44
审稿时长
23 weeks
期刊介绍: Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信