在检查点抑制剂治疗中解读致命毒性作用,使用现实世界药物监测数据和机器学习
Dongxue Yan1, Beibei Lyu1, Jie Yu1
1School of Biomedical Engineering, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
British journal of pharmacology
|September 15, 2025
概括
免疫检查点抑制剂 (ICI) 可以导致致命的免疫相关不良事件 (irAEs). 一个新的机器学习模型,SAFE-ICI,预测了ICI治疗90天内致命的IRAE的短期风险.
科学领域:
- 药物监督 药物监督 药物监督
- 在瘤学瘤学.
- 机器学习 机器学习
背景情况:
- 免疫检查点抑制剂 (ICI) 改善了癌症治疗结果.
- 与免疫相关的不良事件 (irAEs) 是与ICI相关的重大临床挑战.
研究的目的:
- 为了识别与ICI疗法相关的不良事件 (AE) 信号.
- 开发一种机器学习模型 (SAFE-ICI) 来预测ICI治疗的前90天内致命性irrAEs的风险和结果.
主要方法:
- 使用FDA不良事件报告系统进行观察性药监测分析.
- 致命动力学模拟和多变量逻辑回归来分析致命的AE模式.
- 开发和验证SAFE-ICI机器学习框架.
主要成果:
- 在与ICI疗法相关的18个器官系统中确定了358个显著的AE信号.
- PD-1/PD-L1疗法与54次致命的irrAEs相关;组合疗法与20次相关.
- 该SAFE-ICI模型准确地将患者分为致命性irrAEs的低风险和高风险组,显示出不同的生存益处.
结论:
- 机器学习有可能增强药物监管系统.
- SAFE-ICI模型可以帮助临床医生改善ICI治疗期间患者的治疗结果.
相关概念视频
Pharmacovigilance
1.6K
Post-marketing surveillance is a critical component of pharmaceutical regulation, often uncovering unanticipated adverse drug reactions (ADRs) once a drug is widely used over an extended period.
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
1.6K
Therapeutic Drug Monitoring: Affecting Factors
202
Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
202
Therapeutic Drug Monitoring: Overview and Classification
312
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood at designated intervals to ensure the drug concentration stays within a therapeutic range. This monitoring is crucial for optimizing individual dosage regimens, enhancing therapeutic efficacy, and minimizing drug-related toxicity. TDM is vital for drugs with narrow therapeutic windows, significant variability in pharmacokinetics, and a clear correlation between plasma levels and...
312
Therapeutic Drug Monitoring: Drug Analysis Methods
180
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood or body tissues to tailor drug therapy effectively. This monitoring is critical for managing drugs with narrow therapeutic indices like digoxin and phenytoin, ensuring they are both safe and effective. For instance, monitoring theophylline levels in asthma patients involves precision and sensitivity to adjust doses according to individual responses to therapy, ensuring efficacy and...
180
Combination Therapies and Personalized Medicine
5.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.9K
Nonlinear Pharmacokinetics: Overview
1.1K
Nonlinear or dose-dependent pharmacokinetics is a phenomenon that occurs when the pharmacokinetic parameters of certain drugs deviate from linear pharmacokinetics at higher doses. These drugs do not follow the expected first-order kinetics, where the rate of drug elimination is directly proportional to the drug concentration. Instead, they exhibit a nonlinear relationship, which can be attributed to several factors.
Nonlinearity can arise due to the saturation of plasma protein-binding or...
Nonlinearity can arise due to the saturation of plasma protein-binding or...
1.1K


