Infliximab Dosing Strategies and Predicted Trough Exposure in Children With Crohn Disease.

OBJECTIVES

Standard infliximab maintenance dosing of 5 mg/kg every 8 weeks may be inadequate to consistently achieve sufficient drug exposure to minimize loss of response or treatment failure in pediatric Crohn disease (CD). We aimed to determine the predicted infliximab trough concentrations in children with CD during maintenance therapy and the percentage of patients achieving target trough concentration >3 μg/mL.

METHODS

A Monte Carlo simulation analysis was constructed using a published population pharmacokinetic model based on data from 112 children in the REACH trial. We assessed maintenance dosing strategies of 5, 7.5, and 10 mg/kg at dosing intervals of every 4, 6, and 8 weeks for children that differed by age, weight, albumin level, and concomitant immunomodulator therapy.

RESULTS

Based on the index case of a 10-year-old with CD receiving standard infliximab dosing with concomitant immunomodulator therapy, the median (interquartile range) simulated infliximab trough concentration at week 14 was 1.3 (0.5-2.7) μg/mL and 2.4 (1.0-4.8) μg/mL for albumin levels of 3 and 4 g/dL, respectively. Among 1000 simulated children in the model, trough concentration >3 μg/mL at week 14 was achieved 21% and 41% of the time for albumin levels of 3 and 4 g/dL, respectively.

CONCLUSIONS

Standard infliximab maintenance dosing in children with CD is predicted to frequently result in inadequate exposure, especially when albumin levels are low. Optimized dosing strategies for individual patients are needed to achieve sufficient drug exposure during infliximab maintenance therapy.