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Effect of infliximab therapy on serum and fecal biomarker levels in pediatric patients with inflammatory bowel disease

Inflammatory Bowel Disease (IBD), divided into Crohn’s disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC), is a chronic, crippling autoimmune condition characterized by gastrointestinal (GI) inflammation. The methods used to diagnose IBD and assess its activity can be invasive and costly and typically include a combination of histologic, endoscopic, radiologic, clinical, and biochemical measures. Currently, there is an increasing need for the development of noninvasive assessment measures to detect an interval response to prescribed therapy. Previous studies have found serial and fecal biomarkers to be reliable, but non-specific indicators of GI tract inflammation. At present, they cannot be used to distinguish between inflammation resulting from infection and that caused by chronic inflammation in patients with IBD.
The aim of this study is to measure changes in serum and fecal biomarkers over time in individual children and adolescents with CD, UC, and IC initiating infliximab therapy while investigating any parallels between fluctuations in biomarker levels and endoscopic, clinical, and biochemical outcomes. The inflammatory biomarkers evaluated in this study include fecal and serum anti-Saccharomyces-Cerevisiae Antibody (ASCA), fecal and serum lactoferrin, fecal hemoglobin, fecal calprotectin, fecal IL1-α, fecal IL1-β, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR).
The data for this study was collected from a multicenter longitudinal prospective cohort study following pediatric patients over the course of six consecutive infliximab infusion appointments. Study sites include Boston Children’s Hospital and Riley Children’s Hospital in Indianapolis. Participants were recruited from a pool of CD, UC, and IC patients who were either new to infliximab, had been receiving infliximab for less than six months, or had been receiving infliximab for more than one year. Patients brought in stool samples at each of their scheduled infliximab infusions, biochemical labs (ESR and CRP) were obtained, and patients completed a health-related quality of life survey (IMPACT-III Questionnaire).
Forty-three patients (26 with CD, 16 with UC, and one with IC) completed this study. There was no significant difference in mean serum or fecal ASCA levels between participants with CD and those with UC. However, average serum and fecal ASCA were higher in patients with CD than those with UC at almost every infusion. The baseline mean CRP level in patients with CD was significantly higher than that observed in patients with UC (p<0.05). In patients with CD, the mean IMPACT-III score was significantly higher (improved quality of life) at Infusion 5 than at baseline.
The data collected in this study suggest serial biomarker measurements may be useful in monitoring a patient’s response to infliximab therapy. This study is not yet complete and requires further data analysis to more definitively conclude if a single or a composite metric including several fecal and/or serum inflammatory biomarkers would provide a more robust assessment of disease activity in children and young adults with IBD.

Identiferoai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/43351
Date11 November 2021
CreatorsEllis, Montana
ContributorsRufo, Paul A., Wasan, Sharmeel
Source SetsBoston University
Languageen_US
Detected LanguageEnglish
TypeThesis/Dissertation

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