Metabolomics reveal distinct molecular pathways associated with future risk of Crohn's Disease.

Host - microbiome interactions are central to Crohn'sdisease (CD) pathogenesis; yet the early metabolic alterations that precededisease onset remain poorly defined. To explore preclinical metabolicsignatures of CD, we analyzed baseline serum metabolomic profiles in a nestedcase-control study within the Crohn's and Colitis Canada - Genetics, Environment, Microbiome (CCC-GEM) Project, a prospective cohort of 5,122 healthyfirst-degree relatives (FDRs) of CD patients. We included 78 individuals wholater developed CD and 311 matched FDRs who remained disease-free.

Reliability and Responsiveness of Endoscopic Indices for Assessing Crohn's Disease Postoperative Recurrence in the PREVENT trial.

Background And Aims: Assessing endoscopic activity is integral in the management of postoperative Crohn's disease (CD). We aimed to comprehensively characterize the reliability and responsiveness of different endoscopic instruments when used to assess postoperative CD activity.

Methods: Ileocolonoscopy videos (n=70) from the PREVENT trial were reviewed by three blinded central readers.

TYK2 inhibition enhances Treg differentiation and function while preventing Th1 and Th17 differentiation.

Janus kinase (JAK) inhibitors are widely used to inhibit inflammatory cytokine signaling in autoimmune and inflammatory diseases, but their effect on regulatory T cells (Tregs) is poorly characterized. We investigated the effect of a JAK inhibitor, upadacitinib, on human Treg differentiation and phenotype in comparison to BMS-986202, a selective Tyrosine kinase 2 (TYK2) inhibitor. Both upadacitinib and BMS-986202 blocked naive CD4 T cell differentiation into Th1/17 cells, but only BMS-986202 and a related TYK2 inhibitor, deucravacitinib, spared interleukin-2 (IL-2) signaling and Treg induction.

Development and External Validation of an Endoscopic and Histologic Pouchitis Assessment Tool: The Atlantic Pouchitis Index.

Background & Aims: No fully validated indices to measure pouchitis activity exist. We aimed to develop and externally validate a novel endoscopic and histologic index.

Methods: Endoscopists and pathologists used 11 (4 endoscopic, 4 histologic, 3 composite) existing indices and items from a prior Research and Development/University of California Los Angeles appropriateness exercise to assess pouchitis disease activity in videos and images from 98 patients with chronic antibiotic-refractory pouchitis who participated in a randomized placebo-controlled alicaforsen trial.

Real-World Clinical Effectiveness and Safety of Vedolizumab and Ustekinumab in Biologic-Naïve Patients With Early or Late Crohn's Disease: Results From the EVOLVE Expansion Study.

Background: We evaluated the real-world effectiveness and safety of vedolizumab and ustekinumab as first-line biologics in patients with Crohn's disease (CD), by disease duration.

Methods: EVOLVE Expansion (ClinicalTrials.gov, NCT05056441) was a retrospective medical chart review study in Australia, Belgium, and Switzerland.

Real-World Clinical Effectiveness and Safety of Vedolizumab and Ustekinumab in Biologic-Naive Patients With Crohn's Disease By Disease Location: Results from the EVOLVE Expansion Study.

Goals: This analysis compared the real-world effectiveness and safety of vedolizumab versus ustekinumab in biologic-naive patients by CD location.

Background: Crohn's disease (CD) location may affect disease course and treatment decisions.

Study: Medical charts of biologic-naive patients with CD aged 18 years or older initiating vedolizumab or ustekinumab were analyzed in the multicenter, observational, retrospective EVOLVE Expansion study.

Development and validation of a novel Endoscopic ulcer Activity Score for Evaluation of Crohn's Disease (EASE-CD) using data from two randomised controlled trials.

Background: Endoscopy is essential for measuring luminal disease activity in Crohn's disease. Existing indices for evaluating endoscopic Crohn's disease activity are only modestly correlated with clinical disease activity, contain items with ambiguous definitions and poor interobserver reliability, and do not have validated thresholds for defining clinically relevant changes. To address these issues, we conducted a multiphase study to develop and validate a novel endoscopic index for Crohn's disease.

Effectiveness and Safety of Advanced Combination Treatment in Patients With Refractory Inflammatory Bowel Disease or Concomitant Immune-Mediated Disease or Extraintestinal Manifestations: A Multicenter Canadian Study.

Introduction: Owing to the therapeutic ceiling associated with inflammatory bowel disease (IBD) therapies, some patients may require 2 advanced therapeutic agents, known as advanced combination treatment (ACT) to control disease or treat associated extraintestinal manifestations (EIMs).

Methods: We included adult patients with IBD from 9 Canadian centers treated with either 2 biological therapies, a biological plus an oral small molecule, or 2 small molecules. Indications for ACT were the following: (i) refractory IBD, (ii) uncontrolled immune mediated diseases, and (iii) uncontrolled EIMs.

An International Consensus on Appropriate Management of Corticosteroids in Clinical Trials in Inflammatory Bowel Disease.

Background & Aims: Approval of new therapies for inflammatory bowel disease (IBD) requires rigorously designed and well-executed randomized controlled trials (RCTs). Corticosteroids remain a cornerstone of IBD induction therapy, and many patients in trials are enrolled while taking corticosteroids. Despite this, approaches to corticosteroid management in RCTs have been highly heterogeneous, often differing from clinical practice.

Pregnant Pause? Not for IBD Care-A Single Tertiary Care Center Prospective Cohort Study Affirming IBD Management in Pregnancy.

Background: This study examined Inflammatory Bowel Disease (IBD) management and outcomes during pregnancy in a tertiary care setting, focusing on disease activity, medication use, and maternal and neonatal outcomes.

Methods: A prospective cohort study followed 287 women with IBD through 291 pregnancies from 2017 to 2023 at a single tertiary care center, collecting data preconception, during each trimester, and postpartum.

Results: The study observed a 92.

Tofacitinib for Hospitalized Acute Severe Ulcerative Colitis Management (The TRIUMPH Study).

Background: Tofacitinib is a rapidly acting Janus kinase (JAK) inhibitor with increasing evidence of effectiveness in patients with acute severe ulcerative colitis (ASUC). However, there are scarce prospective data analyzing the efficacy and rapidity of action in hospitalized ASUC.

Methods: The TRIUMPH study is a prospective open-label interventional trial of tofacitinib in hospitalized patients with ASUC conducted in 5 hospitals across Canada (Clinicaltrials.

Gut microbiome predictors of advanced therapy response in Crohn's disease: protocol for the OPTIMIST prospective, longitudinal, observational pilot study in Canada.

Introduction: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis, is characterised by chronic and relapsing inflammation of the gastrointestinal tract, leading to significant morbidity and reduced quality of life. The global rise in IBD incidence is driven by a complex interplay of genetic, environmental, dietary and microbiome-related factors. Despite advancements in treatment, such as biologics, response rates remain variable, highlighting the need for personalised approaches.

Directionality of endoscopic and histologic healing in ulcerative colitis: a prospective pilot study.

Objective: Endoscopic and histologic healing in ulcerative colitis (UC) is hypothesized to progress proximally to distally, with healing of the distal rectosigmoid occurring last. However, this has not been empirically verified.

Methods: We performed a prospective cohort study in patients with pancolonic UC commencing treatment with a tumor necrosis factor (TNF) antagonist or vedolizumab.

Symptoms in Persons With Either Active or Inactive Crohn's Disease Are Agnostic to Disease Phenotype: The Magic in Imagine Study.

Background: We aimed to examine the relationship between disease symptoms and disease phenotype in a large Canadian cohort of persons with Crohn's disease (CD).

Methods: Adults (n=1515) with CD from 14 Canadian centers participated in the Mind And Gut Interactions Cohort (MAGIC) between 2018 and 2023. Disease activity was measured using the 24-item IBD Symptom Inventory-Short-Form (IBDSI-SF).

Bile acid-induced metabolic changes in the colon promote Enterobacteriaceae expansion and associate with dysbiosis in Crohn's disease.

Bile acids (BAs) affect the growth of potentially pathogenic commensals, including those from the Enterobacteriaceae family, which are frequently overrepresented in inflammatory bowel disease (IBD). BAs are normally reabsorbed in the ileum for recycling and are often increased in the colonic lumina of patients with IBD, including those with Crohn's disease (CD). Here, we investigated the influence of BAs on gut colonization by Enterobacteriaceae.

Real-world experience and long-term outcomes of a mandatory non-medical switch of adalimumab originator to biosimilars in inflammatory bowel disease.

Background: Over the last decade, the treatment options for inflammatory bowel disease (IBD) have significantly progressed with the emergence of new medications designed to target various immune pathways and mitigate inflammation. Adalimumab (ADA) is a tumor necrosis factor alpha antagonist and stands as an effective treatment for IBD. In April 2021, the province of British Columbia implemented a mandatory non-medical switch policy of the ADA originator Humira to ADA biosimilars.

Motivations behind complementary and alternative medicine use in patients with Crohn's disease and ulcerative colitis.

Background: Complementary and alternative medicine (CAM) use is common in inflammatory bowel disease (IBD) patients and impacts compliance with conventional treatment. Gastroenterologists should understand the motivational factors of CAM use-factors that patients away from standard therapy or towards CAM. Our study describes the motivations behind CAM use for IBD and evaluates differences between Crohn's disease (CD) and ulcerative colitis (UC) patients.

Deployment of an Artificial Intelligence Histology Tool to Aid Qualitative Assessment of Histopathology Using the Nancy Histopathology Index in Ulcerative Colitis.

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by increased stool frequency, rectal bleeding, and urgency. To streamline the quantitative assessment of histopathology using the Nancy Index in UC patients, we developed a novel artificial intelligence (AI) tool based on deep learning and tested it in a proof-of-concept trial. In this study, we report the performance of a modified version of the AI tool.

Outcomes of a mandatory non-medical switch of infliximab to a biosimilar for inflammatory bowel disease in British Columbia, Canada.

Background: Despite infliximab biosimilars becoming widely used in inflammatory bowel disease (IBD) patients, real-world non-medical switching is sparse. A biosimilar non-medical switch was launched in British Columbia in 2019, the first Canadian province to do so, from Remicade to an approved biosimilar (CT-P13 or SB2).

Aims: This study aims to obtain real-world evidence evaluating the clinical outcomes of non-medical switching from Remicade to the infliximab biosimilars.

Practical guidance for managing patients with moderate-to-severe ulcerative colitis using small molecule therapies.

Ulcerative colitis (UC) is a severe and debilitating illness that affects the quality of life and physical health of many Canadians. Given the dynamic and progressive nature of the disease, advanced therapies are required to support its long-term management. The emergence of small molecule therapies offers novel treatment options that target mechanisms central to the immunopathology of UC.

Mucosal Healing With Vedolizumab in Patients With Chronic Pouchitis: EARNEST, a Randomized, Double-Blind, Placebo-Controlled Trial.

Background & Aims: Vedolizumab is indicated for the treatment of chronic pouchitis in the European Union. We assessed whether vedolizumab induced mucosal healing (MH) and if MH was associated with clinical improvements.

Methods: EARNEST, a randomized, double-blind, placebo-controlled study, evaluated vedolizumab efficacy and safety in adults with chronic pouchitis.

Resolution of Rectal Bleeding by Day 7 in Acute Severe Ulcerative Colitis Is Prognostic for Postdischarge Corticosteroid-Free Clinical Remission and Endoscopic Improvement.

This study assesses 2 different disease activity measures, the Modified Truelove Witts Severity Index and the partial Mayo score, in hospitalized patients with acute severe ulcerative colitis (UC) for prediction of postdischarge corticosteroid-free clinical remission and endoscopic improvement to help guide future considerations for disease activity assessment. In this post hoc analysis from the Tofacitinib for Hospitalized Acute Severe Ulcerative Colitis Management (TRIUMPH) trial, these results suggest resolution of the Mayo rectal bleeding subscore may have high prognostic utility and could be considered as a primary end point for hospitalized UC trials. The study underscores the need for further research on patient-reported outcomes and endoscopic indices in larger populations for inpatient UC trials.