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.

An exploratory single-cell analysis of peripheral blood mononuclear cells from vedolizumab-treated Crohn's disease patients identifies response-associated differences among the plasmacytoid dendritic cells and classical monocytes.

Background: Vedolizumab (VDZ) is a monoclonal antibody approved for the treatment of Crohn's disease (CD). Despite its efficacy, non-response to VDZ is common in clinical practice with no clear understanding of how it manifests. Here, we performed an exploratory study characterizing the cellular repertoire of responders and non-responders to VDZ during treatment.

Submucosal hyper-echogenicity on intestinal ultrasound is associated with fat deposition and predicts treatment non-response in patients with ulcerative colitis.

Background And Aims: The submucosa is the most responsive bowel wall layer on intestinal ultrasound (IUS) when assessing treatment response in ulcerative colitis (UC). Submucosal thickening with hyper-echogenicity is observed. This study aimed to quantify echogenicity and understand transmural changes in UC.

Transmural healing in ulcerative colitis patients improves long-term outcomes compared to endoscopic healing alone.

Background & Aims: Endoscopic healing (EH) is recognized as a long-term treatment goal for patients with ulcerative colitis (UC). We investigated whether transmural healing (TH) in UC as assessed by intestinal ultrasound (IUS) is associated with improved outcomes compared to EH alone.

Methods: We performed a retrospective study in a tertiary center on patients with left-sided or extensive UC on stable maintenance treatment who had EH (Mayo Endoscopic Subscore [MES] ≤1) and an IUS performed within six months of an endoscopy with no treatment alterations between IUS and endoscopy.

TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination.

Objectives: Tumour necrosis factor inhibitors (TNFi) are widely used and effective as treatment for immune-mediated inflammatory diseases (IMIDs). However, TNFi therapy causes a faster waning of antibody responses following vaccination. The underlying cause by which TNFi affect humoral immunity remains to be elucidated.

Anti-TL1A antibody, afimkibart, in moderately-to-severely active ulcerative colitis (TUSCANY-2): a multicentre, double-blind, treat-through, multi-dose, randomised, placebo-controlled, phase 2b trial.

Background: TNF-like ligand 1A (TL1A) is an emerging therapeutic target for inflammatory bowel disease. We evaluated the safety and efficacy of multiple doses of afimkibart, a TL1A-directed antibody, in patients with moderately-to-severely active ulcerative colitis.

Methods: The multicentre, double-blind, treat-through, multi-dose, randomised, placebo-controlled, phase 2b, TUSCANY-2 trial was conducted at 114 centres in 23 countries across North America, Europe, Asia, Africa, Australia, and South America.

Efficacy and Safety of Upadacitinib Maintenance Therapy in Patients with Moderately to Severely Active Crohn's Disease: 2-Year Results from the U-ENDURE Long-Term Extension Study.

Background And Aims: The long-term efficacy and safety of upadacitinib in patients with moderate to severe Crohn's disease (CD) were evaluated in the U-ENDURE long-term extension (LTE) study. Here we report the results after 2 years of total maintenance treatment.

Methods: U-ENDURE is an ongoing 240-week LTE study conducted at 243 sites across in 43 countries (first patient enrolled in LTE 21 March 2019).

Comparison of the FDA and EMA guidance on drug development in ulcerative colitis: an expert panel review.

Background And Aims: The Food and Drug Administration (FDA) and European Medicines Agency (EMA) ensure the safety, efficacy, and security of treatments, including therapies for immune-mediated disorders such as inflammatory bowel disease (IBD). Their clinical trial guidelines aid sponsors in designing robust studies. While the EMA updated its guidelines for ulcerative colitis (UC) in 2018, the FDA issued new recommendations in April 2022.

Efficacy and safety of intravenous induction and subcutaneous maintenance therapy with guselkumab for patients with Crohn's disease (GALAXI-2 and GALAXI-3): 48-week results from two phase 3, randomised, placebo and active comparator-controlled, double-blind, triple-dummy trials.

Background: Despite the availability of biological therapies, suboptimal disease control remains a problem for patients with Crohn's disease. We report the results of the GALAXI-2 and GALAXI-3 studies, which aimed to assess the efficacy and safety of intravenous induction followed by subcutaneous maintenance therapy with guselkumab over 48 weeks in adults with moderately to severely active Crohn's disease.

Methods: GALAXI-2 and GALAXI-3 were identically designed, phase 3, randomised, double-blind, triple-dummy, treat-through trials with active and placebo comparators.

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.

Bowel Urgency in Crohn's Disease: Effects of Mirikizumab in a Randomized Controlled Phase 3 Study.

Background And Aims: Bowel urgency (BU) is an underrecognized and debilitating symptom of Crohn's disease. Mirikizumab, an interleukin-23p19 inhibitor, is efficacious for BU resolution in ulcerative colitis. We evaluated the efficacy of mirikizumab in achieving early BU response and remission among participants with Crohn's disease enrolled in the phase 3 VIVID-1 study.

Endoscopic Recurrence in Crohn's Disease Patients With Long-Term Ileostomy.

Background: A small but significant proportion of patients with Crohn's disease (CD) will ultimately require a permanent ileostomy. So far, research has focused primarily on clinical and surgical recurrence rates in the ileum, leaving endoscopic recurrence largely unexplored. The aim of this study was to explore the endoscopic ileal recurrence rate in patients with a long-term ileostomy and to identify potential risk factors.

Development and validation of peripheral blood DNA methylation signatures to predict response to biological therapy in adults with Crohn's disease (EPIC-CD): an epigenome-wide association study.

Background: Biological therapeutics are widely used in Crohn's disease, with evidence of efficacy from randomised trials and real-world experience. Primary non-response is a common, poorly understood problem. We aimed to assess blood methylation as a predictor of response to adalimumab, vedolizumab, or ustekinumab in patients with Crohn's disease.

Point-of-care ultrasound provides useful information in children with Crohn's disease visiting the outpatient clinic.

Objectives: Point-of-care ultrasound (POCUS) is increasingly used in clinical practice. However, it's additional value next to conventional markers of disease activity has not been studied in paediatric Crohn's disease (CD). This study aimed to assess the clinical added value of POCUS in children with CD.

Intestinal Ultrasound and Its Advanced Modalities in Characterizing Strictures in Crohn's Disease.

Background & Aims: Crohn's disease (CD) strictures exhibit varying levels of inflammation and chronicity. We evaluate whether intestinal ultrasound (IUS) is accurate in characterizing stricture composition.

Methods: This prospective, cross-sectional study included patients with CD who underwent IUS prior to a small bowel segment resection.

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.

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.

Quantified motility in Crohn's disease to evaluate stricture composition using cine-MRI.

Objectives: The histopathological composition of a stricture impacts clinical treatment choice. Therefore, imaging biomarkers that can distinguish a predominantly inflammatory from a chronic (i.e.

The position of anti-tumor necrosis factor agents for the treatment of adult patients with Crohn's disease.

Introduction: Tumor Necrosis Factor α (TNF) is a significant systemic inflammatory cytokine in several immune-mediated inflammatory diseases (IMIDs) including inflammatory bowel disease (IBD, Crohn's disease (CD), and ulcerative colitis) and was the first target approved for biologic therapy in IBD.

Areas Covered: This article reviews the efficacy and safety of antiTNF agents for the treatment of CD including specific conditions (e.g.

Immunogenicity and Efficacy of Subcutaneous Infliximab Monotherapy vs Combination Therapy in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Background & Aims: Intravenous (IV) infliximab (IFX) combined with an immunomodulator (combination therapy) outperforms IV IFX monotherapy in terms of clinical, endoscopic, and immunogenicity outcomes in patients with inflammatory bowel disease (IBD). With the advent of subcutaneous (SC) IFX, which is associated with higher serum drug concentrations, it is essential to assess whether SC IFX monotherapy provides similar pharmacokinetic and clinical benefits as combination therapy.

Methods: We conducted a systematic review and meta-analysis (until August 2024), of studies on patients with IBD treated with SC IFX.

Diagnosis and Management of Upper Gastrointestinal Involvement in Adult Patients With Crohn's Disease: A Systematic Review.

Background & Aims: The diagnosis and management of ileocolonic Crohn's disease are well-established. In contrast, standardized guidance pertaining to the diagnosis and management of upper gastrointestinal Crohn's disease (UGICD) is lacking, despite its potentially severe consequences. This comprehensive systematic review describes the prevalence, clinical presentation, and medical and surgical management of involvement of the upper GI tract in adult patients with Crohn's disease.

Deucravacitinib in patients with inflammatory bowel disease: 12-week efficacy and safety results from 3 randomized phase 2 studies in Crohn's disease and ulcerative colitis.

Background And Aims: Tyrosine kinase 2 is a downstream intracellular mediator of interleukin-23 signaling, which has a key role in the pathogenesis of inflammatory bowel disease. Deucravacitinib is a novel, oral, selective, allosteric tyrosine kinase 2 inhibitor currently approved for the treatment of adults with moderate to severe plaque psoriasis.

Methods: Here we describe 3 randomized, double-blind, placebo-controlled phase 2 studies of deucravacitinib in patients with moderately to severely active Crohn's disease (LATTICE-CD [NCT03599622]) or ulcerative colitis (LATTICE-UC [NCT03934216] and IM011-127 [NCT04613518]).