Pharmacokinetic Model Selection for Personalized Infliximab Dosing in IBD

Area of Science:

• Pharmacology
• Immunology
• Biotechnology

Background:

• Infliximab, a monoclonal antibody for immune-mediated diseases, exhibits significant interpatient pharmacokinetic variability.
• This variability necessitates personalized dosing to optimize safety, efficacy, and cost-effectiveness by avoiding prolonged exposure and adverse effects.

Purpose of the Study:

• To identify patient-specific pharmacokinetic models for infliximab.
• To assess the impact of selecting different models on individualized infliximab dosing strategies.

Main Methods:

• Retrospective analysis of adult Crohn's disease patients on infliximab.
• Screening of published pharmacokinetic models and evaluation of model-patient compatibility using Multivariate Exact Discrepancy and Monte Carlo simulations.
• Calculation of median and 90% confidence intervals for doses required to achieve a target infliximab exposure.

Main Results:

• No single pharmacokinetic model was compatible with all patients.
• Dosing recommendations varied significantly across compatible models, highlighting inter-model differences.
• Patient variability contributed to dosing imprecision, with calculated median doses averaging 9.25 mg/kg.

Conclusions:

• A concentration-based method using pharmacokinetic profiling enables personalized infliximab dosing.
• Patients can be categorized based on model compatibility, guiding whether to use manufacturer recommendations or intensified therapeutic drug monitoring.