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Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn's Disease

Authors :
Phillip Minar
Johan Van Limbergen
Brendan M. Boyle
Geert R. D'Haens
Michael J. Rosen
Lee A. Denson
Joshua D. Noe
Jeffrey S. Hyams
Kimberly Jackson
Ruben J. Colman
Yi-Ting Tsai
Gastroenterology and Hepatology
AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
Paediatric Gastroenterology
APH - Digital Health
APH - Health Behaviors & Chronic Diseases
Source :
Inflamm Bowel Dis, Inflammatory bowel diseases, 27(7), 1045-1051. John Wiley and Sons Inc.
Publication Year :
2020

Abstract

Background The neutrophil fecal biomarkers, calprotectin (FCP) and lactoferrin (LCT), and peripheral blood neutrophil CD64 surface receptor (nCD64) are biomarkers for mucosal inflammation in inflammatory bowel disease (IBD). Although FCP has been evaluated as a biomarker for mucosal healing, cut points for LCT and nCD64 are less known. We aimed to identify the cut points for LCT and nCD64 that were associated with FCP remission, with a secondary aim to evaluate the relationship between biochemical outcomes and infliximab (IFX) trough concentrations. Methods We analyzed FCP, LCT, and nCD64 before and after IFX induction in a pediatric Crohn’s disease (CD) cohort study. Week-14 FCP biomarker remission was defined as FCP 17.5 improvement. Predictive outcomes were calculated by receiver operating characteristics (ROCs). Results Among 56 CD patients, ROC analysis identified an infusion 4 LCT 9.4 µg/mL (AUROC, 0.799, P = 0.002) and >11.5 µg/mL (AUROC, 0.835, P = 0.003) were associated with a FCP 5 µg/mL had a median FCP improvement (dose 1 to dose 4) of 90% compared with a median of 35% with levels Conclusions This study establishes cut points in neutrophil stool and blood biomarkers for both biochemical remission and therapeutic trough levels following induction therapy. Further studies that evaluate pharmacodynamic biomarker targets for endoscopic and histologic healing are warranted.

Details

ISSN :
15364844 and 10780998
Volume :
27
Issue :
7
Database :
OpenAIRE
Journal :
Inflammatory bowel diseases
Accession number :
edsair.doi.dedup.....bde9b8ef1798b920085bd06b2f339582