Serum and fecal biomarkers predict response to Infliximab therapy in pediatric patients with Inflammatory Bowel Disease
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Inflammatory Bowel Disease (IBD) is a chronic, idiopathic autoimmune disease characterized by the inflammation of the GI tract. The main subcategories of IBD include Crohn Disease (CD), ulcerative colitis (UC), and Indeterminate Colitis (IC). Currently, IBD is diagnosed and evaluated using clinical, endoscopic, biochemical, and histologic measures - which can be invasive and costly. Previous studies have shown that measurement of serum and fecal inflammatory biomarkers might be effective both for the assessment of intestinal infectious or inflammatory processes, as well as for gauging IBD disease activity. Inflammatory biomarkers investigated in this study include serum and fecal Anti-Saccharomyces-Cerevisiae Antibody (ASCA), serum and fecal lactoferrin, fecal calprotectin, fecal hemoglobin, IL1-𝛼, IL1-β, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). IMPACT-III questionnaires are utilized to measure the quality of life in enrolled subjects. Data collected in this study investigated the relationship between changes in serum and fecal biomarker levels, clinical disease activity, and the mental wellbeing of patients. The primary objective was to measure changes in inflammatory biomarker levels in patients with CD, UC, and IC after being treated with the anti-TNF therapy Infliximab (Remicade). The second objective is to study the relationship between changes in these biomarker levels and the clinical, biochemical, and endoscopic outcome parameters of IBD in patients. This is a multicenter, longitudinal, cohort study following 50 pediatric patients with IBD over the course of six Remicade infusion appointments. The project was conducted in partnership with Riley’s Children Hospital in Indianapolis. Patients with CD, UC, and IC were recruited for the study and stratified with respect to the temporal phase of their Remicade infusions, including: • Induction • Past induction, but less than 6 months • Those who have been receiving Remicade for over one year. A total of 58 eligible IBD patients are currently enrolled. 13 patients have withdrawn from the study, leaving 45 active patients: 27 CD, 17 UC, and 1 IC remaining in the prospective cohort. Patients provided serum and fecal samples and completed IMPACT-III questionnaires at the time of each Remicade infusion. Baseline serum ASCA levels were 0.014 ±0.029 OD from (n=15) patients with CD, 0.0083 ±0.022 OD in (n=12) patients with UC, and 0.002 OD in one patient with IC. Baseline fecal ASCA levels were 0.068 ±0.186 OD in (n=10) patients with CD, 0.0018 ±0.0013 OD in (n=9) patients with UC, and 0.001 OD in one patient with IC. At both baseline and at the time of the first infusion, CRP levels were significantly higher in patients with CD (p<0.05). At the time of the first infusion, the ESR in patients with CD was significantly higher than that in patients with UC (p<0.10). Serum lactoferrin was significantly higher in patients with UC at infusion 2 (p<0.05). ESR was significantly higher in patients with UC (p<0.10) at their fourth infusion. Our data support the hypothesis that serum and fecal biomarkers are useful in evaluating the response of intestinal inflammation to Remicade therapy. This study is ongoing, and further sample collection and data analysis are needed to more conclusively determine the accuracy of inflammatory biomarkers as a diagnostic tool for use in the diagnosis and interval assessment of patients with IBD.