Development of Infliximab Target Concentrations During Induction in Pediatric Crohn Disease Patients

摘要

Objectives: Subtherapeutic drug concentrations contribute to both primary and secondary nonresponse to infliximab in children with Crohn disease (CD). The aim of this study was to evaluate treatment outcomes and infliximab concentrations at infusions 2 and 3 with an objective to establish infliximab targets during induction for primary responders. Methods: Single-center, prospective cohort of anti- tumor necrosis factor-alpha naive CD patients younger than 22 years starting infliximab. Clinical response was defined with the weighted pediatric CD activity index at the fourth infusion. Rates of biological response (>50% improvement in fecal calprotectin) and maintenance concentrations >= 5 mu g/mL were secondary outcomes. Results: We enrolled 72 patients with CD with 70 of 72 receiving infliximab monotherapy. Clinical response, biological response, and start of maintenance concentrations >= 5 mu g/mL were achieved in 64%, 54%, and 22%, respectively. The median (interquartile range) infliximab concentrations at infusion 2 and 3 in clinical responders were 27.8 mu g/mL (19.5-40) and 14 mu g/mL (8.3-24) compared to 18.8 mu g/mL (9.1-23, P = 15.9 mu g/mL at infusion 3 was associated with clinical response (area under the curve [AUC] 0.73), whereas an infusion 3 level >= 18 mu g/mL was associated with a start of maintenance concentration >5 mu g/mL (AUC 0.85). Independent predictors for infusion 3 levels = 29 mu g/mL) and infusion 3 (>= 18 mu g/mL) infliximab concentrations were strongly associated with improved early outcomes and higher first maintenance dose levels.