Pharmacokinetic Model Selection for Personalized Infliximab Dosing in IBD

Infliximab, a monoclonal antibody used for immune-mediated diseases, shows high interpatient pharmacokinetic variability. Prolonged exposure increases the risk of adverse effects and costs, making dose personalization essential to balance safety, efficacy, and cost-effectiveness. Population pharmacokinetic models support individualized dosing, but different models may predict varying drug exposure for the same patient. This study aims to identify compatible models for each patient and assess the impact of model selection on dosing. This retrospective study included adult Crohn's disease patients receiving infliximab. Published pharmacokinetic models were screened. Model-patient compatibility was evaluated using Multivariate Exact Discrepancy through 100,000 Monte Carlo simulations. The Metropolis-Hastings algorithm generated individual parameter distributions. For each model-patient pair, the median and 90% confidence interval of the dose required to achieve a target exposure of 2079 mg*day/L were computed. Sixteen models were tested. No model was compatible with all patients. Dosing was calculated only for compatible pairs. The average median dose was 9.25 mg/kg, with an average imprecision of 6.63 mg/kg. The highest median dose reached 23.21 mg/kg, reflecting inter-model differences, while the greatest imprecision (25.69 mg/kg) stemmed from patient variability. This concentration-based method personalizes dosing via pharmacokinetic profiling. Patients can be classified into three groups: (1) those for whom all models provide similar recommendations, indicating high reliability across models; (2) those incompatible with all models, for whom the posology recommended by the manufacturer should be prioritized; and (3) those for whom some models are compatible but intensified therapeutic drug monitoring is required.