Details

Autor(en) / Beteiligte

• Clarkston, Kathryn
• Tsai, Yi‐Ting
• Jackson, Kimberly
• Rosen, Michael J.
• Denson, Lee A.
• Minar, Phillip

Titel

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

Ist Teil von

• Journal of pediatric gastroenterology and nutrition, 2019-07, Vol.69 (1), p.68-74

Ort / Verlag

United States: by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.