Ultrasound and Proteomics for Guselkumab Response Assessment in Crohn's Disease (UPGRADE).

UPGRADE: Ultrasound and Proteomics for Guselkumab Response Assessment in Crohn's Disease.

The goal of this observational study is to evaluate the response of guselkumab in adult patients with Crohn's disease (CD) as measured on intestinal ultrasound (IUS), the relative quantities of CD64 in endoscopic tissue biopsies, and the protein signature in the blood of patients with and without therapy response. The main question it aims to answer is:

• What is the proportion of ileal Crohn's disease patients with and without strictures who achieve an intestinal ultrasound response?
• What is the quantity of CD64 in tissue in CD patients at baseline and at week 52 with and without IUS response?
• Are there proteomic signatures in blood of CD patients that respond to GUS?

This is a prospective, single-centre observational study conducted at conducted at the University of Calgary and the University of Alberta. All patients with histologically confirmed distal ileal CD with or without colonic involvement initiating guselkumab (GUS) will be consecutively enrolled. Patients will be sub-divided into the following phenotypes: 1) Stricture: Bowe wall thickness > 3 mm, luminal apposition < 1cm and prestenotic dilation of distal ileum, or 2) Non-Stricture (inflammatory): ileal CD with no evidence of stricture on intestinal ultrasound (IUS) or prior cross-sectional imaging.

Recruited patients providing informed consent will undergo IUS within 14 days of GUS start with blood collection prior to GUS start. Blood collection and IUS will be performed at weeks 0, 12, 24, and 52. Length of visit windows will be within 14 days of study visit due date. Gastroenterologists with bowel sonography expertise will perform standard of care IUS on all consented CD patients meeting inclusion criteria in clinic at baseline, weeks 12, 24, and 52. Colonoscopy will be performed in all patients at baseline and between week 48 and 52 with segmental biopsies for proteomic and CD64 analysis. For tissue CD64 quantification, a single-cell suspension will be obtained using collagenase type 4 and deoxyribonuclease I for enzymatic digestion followed by mechanical dissociation. CD64 will be tagged using the same markers as described for serum, and samples will be submitted to flow cytometry at the local university facility (Calgary or Alberta). Serum will be collected for proteomic analysis at baseline and week 52.

Inclusion Criteria:

Male or female, 18 to 80 years old

BWT on IUS > 3.0mm in the ileum and colonic disease permitted.

Patients naïve to guselkumab.

Stricture phenotype - BWT > 3 mm, luminal apposition < 1cm or < 50% of adjacent normal bowel diameter, and prestenotic dilation of distal ileum. Naïve or anastomotic strictures permitted.

Non-stricture phenotype- ileal CD with no evidence of stricture on IUS, computed tomography enterography (CTE), or magnetic resonance enterography (MRE), ever or fistulizing phenotype.

Exclusion Criteria:

Pregnancy

Ileostomy or colostomy

Significant obesity (BMI > 35)

Contraindications to initiating GUS such as active infection.

Active malignancy within five years.

Conditions with fibrosis involving other organs such as lungs, kidneys, brain, or skin.