文章：

美国食品药品监督管理局批准靶向抗癌药物后发布新的严重安全警告

New Serious Safety Warnings for Targeted Anticancer Agents After Their Initial FDA Approval

原文发布日期：8 February 2025

DOI: 10.3390/cancers17040584

类型: Article

开放获取: 是

英文摘要：

Background:New safety concerns about targeted anticancer agents (TAAs) often emerge in the first few years after their initial regulatory approval. Our aim was to determine whether new serious and potentially fatal adverse drug reactions (ADRs) continue to emerge in the updated drug labels of TAAs several years after their initial regulatory approval and whether their emergence can be predicted.Methods:The updated drug labels of TAAs approved by the U.S. Food and Drug Administration before July 2013 were analyzed. Serious and potentially fatal ADRs were identified in the Warnings & Precautions (WPs) and Boxed Warnings (BWs) sections of the updated drug labels. Generalized linear mixed models were used to examine the associations between the number of adverse drug reactions and time, drug type (small molecules vs. monoclonal antibodies), and the availability of companion diagnostics for biomarkers.Results:Among 37 eligible TAAs, 25 (68%) were small molecules and 11 (30%) had available companion diagnostics for the biomarkers. Time was a significant predictor of new WPs (p˂ 0.001) and BWs (p= 0.008). The updated drug labels of the small molecules received significantly more new WPs (p= 0.042) as compared to monoclonal antibodies. The availability of the companion diagnostics for the biomarkers did not have an impact on the emergence of new ADRs.Conclusions:New serious ADRs of TAAs continue to emerge in updated drug labels several years after their initial regulatory approval. Oncologists, regulators, and payers should be aware of the changing risk–benefit ratios of approved TAAs.

摘要翻译： 

背景：靶向抗癌药物（TAAs）在获得初步监管批准后的最初几年内，常出现新的安全性问题。本研究旨在探究TAAs在获得初步监管批准数年后，其更新的药品标签中是否持续出现新的严重且可能致命的药物不良反应（ADRs），以及这些不良反应的出现是否可预测。 方法：分析了美国食品药品监督管理局在2013年7月前批准的TAAs的更新药品标签。在更新标签的“警告与注意事项”（WPs）和“黑框警告”（BWs）部分识别严重且可能致命的ADRs。采用广义线性混合模型检验药物不良反应数量与时间、药物类型（小分子药物 vs. 单克隆抗体）以及生物标志物伴随诊断可用性之间的关联。 结果：在37种符合条件的TAAs中，25种（68%）为小分子药物，11种（30%）具有可用的生物标志物伴随诊断。时间是预测新WPs（p < 0.001）和新BWs（p = 0.008）的显著因素。与单克隆抗体相比，小分子药物的更新药品标签中新增WPs的数量显著更多（p = 0.042）。生物标志物伴随诊断的可用性对新ADRs的出现没有影响。 结论：TAAs在获得初步监管批准数年后，其更新的药品标签中仍持续出现新的严重ADRs。肿瘤科医生、监管机构和支付方应关注已批准TAAs风险-获益比的变化。

原文链接：

New Serious Safety Warnings for Targeted Anticancer Agents After Their Initial FDA Approval