PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
The Combination of Predictive Factors of Pharmacokinetic Origin Associates with Enhanced Disease Control During Treatment of Pediatric Crohn’s Disease with Infliximab
Dubinsky, M.C.; Rabizadeh, S.; Panetta, J.C.; Spencer, E.A.; Everts-van der Wind, A.; Dervieux, T. The Combination of Predictive Factors of Pharmacokinetic Origin Associates with Enhanced Disease Control during Treatment of Pediatric Crohn’s Disease with Infliximab. Pharmaceutics2023, 15, 2408.
Dubinsky, M.C.; Rabizadeh, S.; Panetta, J.C.; Spencer, E.A.; Everts-van der Wind, A.; Dervieux, T. The Combination of Predictive Factors of Pharmacokinetic Origin Associates with Enhanced Disease Control during Treatment of Pediatric Crohn’s Disease with Infliximab. Pharmaceutics 2023, 15, 2408.
Dubinsky, M.C.; Rabizadeh, S.; Panetta, J.C.; Spencer, E.A.; Everts-van der Wind, A.; Dervieux, T. The Combination of Predictive Factors of Pharmacokinetic Origin Associates with Enhanced Disease Control during Treatment of Pediatric Crohn’s Disease with Infliximab. Pharmaceutics2023, 15, 2408.
Dubinsky, M.C.; Rabizadeh, S.; Panetta, J.C.; Spencer, E.A.; Everts-van der Wind, A.; Dervieux, T. The Combination of Predictive Factors of Pharmacokinetic Origin Associates with Enhanced Disease Control during Treatment of Pediatric Crohn’s Disease with Infliximab. Pharmaceutics 2023, 15, 2408.
Abstract
Objective: 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. Methods: PF of PK origin were evaluated from two cohorts, the first received standard dosing (n=37), and the second was designed to proactively target therapeutic IFX concentrations (n=108). Concentrations were measured using homogenous mobility shift assay. Clearance was estimated using nonlinear mixed effects methods with Bayesian priors. C-reactive protein based clinical remission (<3mg/L in the absence of symptoms) was used for the disease control outcome. Longitudinal changes in disease control due to factors including time, IFX concentration, and clearance were analyzed using repeated event analysis. Change in objective function value (∆OFV) was calculated to compare concentration and clearance. Results: Lower baseline clearance and proactive dosing associated with enhanced disease control during induction (p<0.01). Higher IFX concentrations and lower Clearance measured at the second, third and fourth infusion yielded improved disease control during maintenance (p<0.032). During maintenance, the association with disease control was better with clearance than with concentrations (∆OFV= -19.2; p<0.001), and the combination of both further minimized OFV (p<0.001) with markedly improved clinical yield in the presence of both PF of PK origin. Conclusion: PF of PK origin and lower clearance during induction and maintenance yielded enhanced disease control in pediatric CD treated with IFX. The combination of IFX concentration and clearance are better predictors of therapeutic outcome compared to either one alone.
Medicine and Pharmacology, Medicine and Pharmacology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
