Project Details

Leveraging Molecular Discovery to Guide Precision Dosing for Children with Crohn’s Disease

Ruben Colman, MD, MS

Summary

BACKGROUND: Crohn’s disease is a chronic progressive disease that can affect any part of the GI gastrointestinal tract. There is only one drug class (anti-TNF therapy) that is approved to treat children with Crohn’s disease, and if it is not used correctly it can result in irreversible disease complications. GAP: There is a high unexplained variability in drug response and drug clearance for anti-TNF therapy. This results in a high rate of drug failure and limited drug durability in this population. HYPOTHESIS: I hypothesize that the incorporation of novel microbes and metabolites into conventional monitoring strategies is superior to conventional monitoring alone in predicting endoscopic healing after anti-TNF therapy. METHODS: This is an analysis of a multicenter prospective cohort study in which we collected biosamples (blood, stool and intestinal biopsies) from children with Crohn’s disease who are starting anti- TNF therapy. We will analyze the relationship between microbiome and metabolome signatures and pharmacologic factors among these subjects. RESULTS: Pending. IMPACT: Novel biomarker signatures identified in this project can be prospectively used to help guide dosing decisions among patients with Crohn’s disease to prevent early drug failure and disease complications.