Crohn’s & Colitis Congress™

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P036 - EXPLORING EARLY-RESPONSIVE PHARMACODYNAMIC BIOMARKERS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE (IBD) (Room Poster Session)

PURPOSE: The generation of high-quality pilot data that leads to “go/no-go decisions” regarding new or repurposed drugs is often problematic, particularly with a high placebo response rate. In short duration trials, pharmacodynamic (PD) biomarkers can demonstrate proof-of-concept of drug action that may or may not be bridged to clinical outcomes. We sought to identify early-changing PD biomarkers in patients with IBD. METHODS: Clinical scores and serum were obtained at baseline and after 1-2 weeks of corticosteroids in 5 IBD patients. Using the SOMAscan assay, 45 published chronic steroid and infliximab-responsive proteins were evaluated. All were log-transformed and normality verified using the Shapiro-Wilk test. Pre- to post- treatment comparisons were performed using a paired t-test (p<0.01). Label-free proteome profiling using mass spectrometry was performed. RESULTS: Thirteen proteins responded consistently to 1-2 weeks of corticosteroids. These included biomarkers previously shown to be responsive in pediatric IBD patients after 2 doses of infliximab (CCL23, carnosinase, p-cadherin, CCL25, testican-2, AGT, and FAM3B) and after longer courses of corticosteroid therapy (AGT, afamin, GHBP, CCL22, MMP12, PROT C, Ly9). Four were detected by label-free mass spectrometry (AGT, afamin, PROT C, and carnosinase). Most are involved in regulation of inflammation, immune homeostasis, and extracellular matrix binding. In this small sample, change in some biomarkers correlated with short-term clinical response (carnosinase, testican-2, FAM3B). CONCLUSIONS: We have identified treatment-responsive proteins in IBD patients after several weeks of steroids, after 2 doses of infliximab, and within 1-2 weeks of treatment with steroids; these biomarkers may be useful for screening trials of anti-inflammatory drugs. For selection of candidates to study in larger, controlled trials, short-duration biomarker-based trials would be beneficial for patients.