Triangular Phenotyping and Response Assessment in Small Bowel Crohn's Disease Using Magnetic Resonance Enterography (MRE) and Novel Proteomic Biomarkers
The small bowel (SB) is involved in \ 70% of patients with Crohn's disease (CD). There is an unmet need for accurate and clinically meaningful methods to measure small bowel Crohn's Disease (SBCD) activity. This is particularly relevant as the field moves towards treat-to-target management strategies. The overall objective of this proposal is to establish that radiologic transmural response (TR) and a novel proteomic biomarker are accurate and clinically meaningful predictors of SBCD inflammatory activity and response to biologic therapy. To address this objective, we will establish a prospectively followed cohort of SBCD patients starting a new biologic therapy. These patients will be comprehensively phenotyped using state of the art MRE imaging, proteomic profiling and clinical disease activity indices. We will use this innovative approach of triangular phenotyping to address our central hypothesis that Corticosteroid-free remission at 52 weeks after biologic therapy initiation is predicted by short term radiologic TR or early changes in serum proteomic biomarker profiles. Serum proteomic biomarker profiles will be evaluated using SOMAscanTM (SomaLogic, Inc., Boulder, Colorado, USA), a novel platform allowing high-throughput analysis of proteins through Slow Off-rate Modified DNA Aptamer (SOMAmer)-based capture array. Our preliminary data using SOMAscan identified a panel of 12 serum proteins whose differential expression pattern from Week 0 to week 6 after starting a biologic can predict week 14 clinical remission in SBCD patients. The significance of this proposal is that the development of an early predictive model using radiological and serum endpoints will facilitate a personalized algorithmic approach to identify patients with SBCD who will benefit from treatment escalation or change to a different biologic. Furthermore, it will be used to generate a tangible career tool of a prospectively enrolled patient cohort to further study radiologic and biomarker predictors of response in SBCD. This award will also enhance the career of the principal investigator by facilitating acquisition of an enhanced skill set in clinical research, bioinformatics and biomarker discovery.
• Patient who have had a prior standard of care (SOC) ileocolonoscopy with biopsies confirming SBCD
• And with active disease visible on a baseline MRE (small bowel only or ileocolonic disease)
• And are being initiated on a biologic (anti-TNFs, vedolizumab and ustekinumab) approved for CD, regardless of their prior biologic exposure, will be recruited.
• Prior studies have confirmed active SBCD noted on MRE as consistent with active disease using histopathology as reference standard.45