Open AccessDevelopment of Infliximab Target Concentrations During Induction in Pediatric Crohn Disease Patients
Author(s) -
Clarkston Kathryn,
Tsai YiTing,
Jackson Kimberly,
Rosen Michael J.,
Denson Lee A.,
Minar Phillip
Publication year - 2019
Publication title -
journal of pediatric gastroenterology and nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 131
eISSN - 1536-4801
pISSN - 0277-2116
DOI - 10.1097/mpg.0000000000002304
Subject(s) - infliximab , medicine , interquartile range , gastroenterology , calprotectin , prospective cohort study , prednisone , crohn's disease , therapeutic drug monitoring , inflammatory bowel disease , pharmacokinetics , tumor necrosis factor alpha , disease
ABSTRACT 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 naïve 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 μg/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 μg/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 μg/mL (19.5–40) and 14 μg/mL (8.3–24) compared to 18.8 μg/mL (9.1–23, P < 0.001) and 7.8 μg/mL (4–13.2, P < 0.01) in nonresponders. Receiver operating characteristic analysis determined that an infliximab concentration ≥15.9 μg/mL at infusion 3 was associated with clinical response (area under the curve [AUC] 0.73), whereas an infusion 3 level ≥18 μg/mL was associated with a start of maintenance concentration >5 μg/mL (AUC 0.85). Independent predictors for infusion 3 levels <18 μg/mL included pretreatment prednisone, low body mass index, elevated erythrocyte sedimentation rate and C‐reactive protein, hypoalbuminemia, and an infusion 2 infliximab level <29 μg/mL. Conclusions: We found that infusion 2 (≥29 μg/mL) and infusion 3 (≥18 μg/mL) infliximab concentrations were strongly associated with improved early outcomes and higher first maintenance dose levels.