Review and External Evaluation of Population Pharmacokinetic Models for Vedolizumab in Patients with Inflammatory Bowel Disease: Assessing Predictive Performance and Clinical Applicability

作者：Marija Jovanović, Ana Homšek, Srdjan Marković, Đorđe Kralj, Petar Svorcan, Tamara Knežević Ivanovski, O Odanovic, Katarina Vučićević · 发表于：Biomedicines · 年份：2024 · DOI：10.3390/biomedicines13010043 · 被引用次数：3 · 研究领域：Inflammatory Bowel Disease、Biosimilars and Bioanalytical Methods、Rheumatoid Arthritis Research and Therapies

BACKGROUND/OBJECTIVES: Several population pharmacokinetic models of vedolizumab (VDZ) are available for inflammatory bowel disease (IBD) patients. However, their predictive performance in real-world clinical settings remains unknown. This study aims to externally evaluate the published VDZ pharmacokinetic models, focusing on their predictive performance and simulation-based clinical applicability. METHODS: A literature search was conducted through PubMed to identify VDZ population pharmacokinetic models. A total of 114 VDZ concentrations from 106 IBD patients treated at the University Medical Center "Zvezdara", Republic of Serbia, served as the external evaluation cohort. The predictive performance of the models was assessed using prediction- and simulation-based diagnostics. Furthermore, the models were utilized for Monte Carlo simulations to generate concentration-time profiles based on 24 covariate combinations specified within the models. RESULTS: Four published pharmacokinetic models of VDZ were included in the evaluation. Using the external dataset, the median prediction error (MDPE) ranged from 13.82% to 25.57%, while the median absolute prediction error (MAPE) varied between 41.64% and 47.56%. None of the models fully met the combined criteria in the prediction-based diagnostics. However, in simulation-based diagnostics, pvcVPC showed satisfactory results, despite wide prediction intervals. Analysis of NPDE revealed that only the models by Rosario et al. and Okamoto e...