The Combination of Predictive Factors of Pharmacokinetic Origin Associates with Enhanced Disease Control during Treatment of Pediatric Crohn’s Disease with Infliximab

Abstract

Infliximab (IFX) concentrations are a predictive factor (PF) of pharmacokinetic (PK) origin in the treatment of Crohn’s disease (CD). We evaluated Clearance, another PF of PK origin, either alone or in combination with concentrations. They were evaluated from two cohorts, the first designed to receive standard dosing (n = 37), and the second designed to proactively target therapeutic IFX concentrations (n = 108). Concentrations were measured using homogeneous mobility shift assay. Clearance was estimated using the nonlinear mixed effects methods with Bayesian priors. C-reactive protein-based clinical remission (p p p p < 0.001) with markedly improved clinical yield in the presence of both PF of PK origin. We conclude that the combination of IFX concentration and Clearance are better predictors of therapeutic outcome compared with either one alone.

Keywords

• infliximab
• Crohn’s disease
• pharmacokinetics
• clearance
• predictive factors