Performance of Eight Infliximab Population Pharmacokinetic Models in a Cohort of Dutch Children with Inflammatory Bowel Disease.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Clinical Pharmacokinetics Pub Date : 2024-04-01 Epub Date: 2024-03-15 DOI:10.1007/s40262-024-01354-7
Nanja C Bevers, Ron J Keizer, Dennis R Wong, Arta Aliu, Marieke J Pierik, Luc J J Derijks, Patrick F van Rheenen
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引用次数: 0

Abstract

Background and objective: Efficacy of infliximab in children with inflammatory bowel disease can be enhanced when serum concentrations are measured and further dosing is adjusted to achieve and maintain a target concentration. Use of a population pharmacokinetic model may help to predict an individual's infliximab dose requirement. The aim of this study was to evaluate the predictive performance of available infliximab population pharmacokinetic models in an independent cohort of Dutch children with inflammatory bowel disease.

Methods: In this retrospective study, we used data of 70 children with inflammatory bowel disease (443 infliximab concentrations) to evaluate eight models that focused on infliximab pharmacokinetic models in individuals with inflammatory bowel disease, preferably aged ≤ 18 years. Predictive performance was evaluated with prior predictions (based solely on patient-specific covariates) and posterior predictions (based on covariates and infliximab trough concentrations). Model accuracy and precision were calculated with relative bias and relative root mean square error and we determined the classification accuracy at the trough concentration target of ≥ 5 mg/L.

Results: The population pharmacokinetic model by Fasanmade was identified to be most appropriate for the total dataset (relative bias before/after therapeutic drug monitoring: -20.7%/11.2% and relative root mean square error before/after therapeutic drug monitoring: 84.1%/51.6%), although differences between models were small and several were deemed suitable for clinical use. For the Fasanmade model, sensitivity and specificity for maximum posterior predictions for the next infliximab trough concentration to be ≥ 5 mg/L were respectively 83.5% and 80% with an area under the receiver operating characteristic curve of 0.870.

Conclusions: In our paediatric cohort, various models provided acceptable predictive performance, with the Fasanmade model deemed most suitable for clinical use. Model-informed precision dosing can therefore be expected to help to maintain infliximab trough concentrations in the target range.

Abstract Image

八种英夫利西单抗群体药代动力学模型在荷兰炎症性肠病儿童队列中的表现
背景和目的:如果能测定血清中英夫利西单抗的浓度,并进一步调整剂量以达到并维持目标浓度,就能提高英夫利西单抗对炎症性肠病患儿的疗效。使用群体药代动力学模型有助于预测个体的英夫利西单抗剂量需求。本研究旨在评估现有英夫利西单抗群体药代动力学模型在荷兰炎症性肠病儿童独立队列中的预测性能:在这项回顾性研究中,我们使用了 70 名炎症性肠病患儿的数据(443 例英夫利西单抗浓度),对 8 个模型进行了评估,这些模型主要针对炎症性肠病患儿的英夫利西单抗药动学模型,年龄最好小于 18 岁。通过先验预测(仅基于患者特异性协变量)和后验预测(基于协变量和英夫利西单抗谷浓度)对预测性能进行了评估。用相对偏差和相对均方根误差计算了模型的准确度和精确度,并确定了谷浓度目标值≥5 mg/L时的分类准确度:结果:Fasanmade 的群体药代动力学模型被认为最适合整个数据集(治疗药物监测前/后的相对偏差:-20.7%/11.2%,治疗药物监测前/后的相对均方根误差:84.1%/51.6%):尽管各模型之间的差异很小,但有几个模型被认为适合临床使用。对于 Fasanmade 模型,下一次英夫利西单抗谷浓度≥ 5 mg/L 的最大后验预测灵敏度和特异度分别为 83.5%和 80%,接收者工作特征曲线下面积为 0.870:在我们的儿科队列中,各种模型都提供了可接受的预测性能,而 Fasanmade 模型被认为最适合临床使用。因此,以模型为依据的精确给药有望帮助将英夫利西单抗的谷浓度维持在目标范围内。
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来源期刊
CiteScore
8.80
自引率
4.40%
发文量
86
审稿时长
6-12 weeks
期刊介绍: Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
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