{Reference Type}: Journal Article
{Title}: Infliximab in paediatric inflammatory bowel disease: External evaluation of population pharmacokinetic models.
{Author}: Heikal OS;van Rheenen PF;Touw DJ;Kosterink JGW;Maurer M;Koomen JV;Chelle P;Mian P;
{Journal}: Br J Clin Pharmacol
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 6
{Factor}: 3.716
{DOI}: 10.1111/bcp.16126
{Abstract}: <B>OBJECTIVE: </B>Use of infliximab (IFX) has improved outcomes in children with inflammatory bowel disease (IBD). However, a proportion of patients does not respond to IFX or loses response over time. Population pharmacokinetic (PopPK) modelling is a promising approach for IFX dose optimization, but with the increasing number of PopPK models in literature, model evaluation is essential. The aims of this study are: (i) to validate the predictive performance of existing IFX PopPK models using a cohort of children with IBD; and (ii) to perform a Bayesian estimation of the most suitable model to predict the next IFX concentrations.<BR><B>METHODS: </B>PubMed was searched for IFX PopPK models in children. Selected models were rebuilt and analysed using R. Model performance was assessed through goodness-of-fit-plots, residuals against time, prediction error and prediction-corrected visual predictive checks. The validation cohort consisted of 73 children with IBD who were treated with IFX in our centre between 2017 and 2023 (340 IFX measurements).<BR><B>RESULTS: </B>We identified 9 PopPK models. Model bias for individual predicted values ranged from -9.29% to 8.01% compared to bias for population predicted values. The model by Vande Casteele et al. demonstrated superior performance (individual predicted bias 2.13, population predicted bias -6.11); upon Bayesian estimation, it predicted induction trough levels with median error of 12.95% but had a median error of -69% predicting maintenance concentrations.<BR><B>CONCLUSIONS: </B>The model by Vande Casteele et al. displayed superior performance in initial evaluations but had a high error in estimating next IFX levels and can only be used in practice to predict induction levels.