International Magnetic Resonance Imaging Consensus for use in Luminal Crohn's Disease Trials and Clinical Practice.

Background And Aims: Cross sectional imaging is an integral part of evaluating disease activity and complications in Crohn's disease. There remains a need to develop guidance that may be for both clinical trials and clinical practice. This initiative aimed to develop consensus statements for definitions of response and remission, transmural healing, optimal timing for assessing, and evaluation of treatment efficacy in patients with Crohn's disease using magnetic resonance enterography (MRE) in clinical trials and clinical practice.

Asia Pacific association of gastroenterology consensus statements on histopathological evaluation of inflammatory bowel diseases.

Background: Mucosal histological activity is increasingly valued as a treatment endpoint in inflammatory bowel diseases (IBD). In the Asia Pacific region, the utility and acceptability of IBD histology as a treatment endpoint are uncertain due to the heterogeneity of IBD prevalence, resourcing and level of knowledge among practitioners. There is an opportunity to engage clinicians to harmonise histology reporting and collaborate with pathologists in this field.

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.

Early Infliximab Levels and Clearance Predict Outcomes After Infliximab Rescue in Acute Severe Ulcerative Colitis: Results From PREDICT-UC.

Background & Aims: The role of infliximab therapeutic drug monitoring in acute severe ulcerative colitis (ASUC) management is unknown. We aimed to identify whether infliximab therapeutic drug monitoring is associated with ASUC outcomes.

Methods: Serum and stool samples were collected from patients enrolled in the PREDICT-UC randomized controlled trial (NCT02770040), which compared intensified and standard infliximab rescue in steroid-refractory ASUC.

Endocytoscopy in real-time assessment of histological and endoscopic activity in ulcerative colitis.

Background: Endocytoscopy is an advanced imaging modality that provides real-time, ultra-high magnification views of the intestinal mucosa. In ulcerative colitis (UC), the combined assessment of endoscopic and histological remission is now becoming a standard practice. However, histological evaluation typically falls outside the scope of the endoscopist.

Clinical Trial: Association Between Early Disease Clearance and Long-Term Outcomes-4-Year Results From the Phase 3 UNIFI Study of Ustekinumab in Ulcerative Colitis.

Background: Achievement of disease clearance (simultaneous symptomatic remission and histo-endoscopic mucosal improvement [HEMI]) following induction therapy may lead to better long-term outcomes in ulcerative colitis (UC).

Aim: To evaluate disease clearance in the phase 3 UNIFI program and its association with long-term outcomes.

Methods: UNIFI comprised randomised, placebo-controlled induction and maintenance studies and a long-term extension, which evaluated intravenous ustekinumab induction (130 mg or ~6 mg/kg) and subcutaneous ustekinumab maintenance therapy (90 mg every 8 or 12 weeks) through 4 years in patients with UC.

Meta-Analysis: Intravenous Versus Subcutaneous Infliximab in Inflammatory Bowel Disease.

Background: Subcutaneous infliximab may provide multiple benefits over intravenous formulations. However, there is uncertainty about the relative efficacy in inflammatory bowel disease (IBD).

Aim: To evaluate the relative efficacy of intravenous versus subcutaneous infliximab in patients with IBD using clinical response, clinical remission, and endoscopic remission outcomes at 30- and 54-week outcomes.

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.

Diagnostic Accuracy of Noninvasive Biomarkers and Imaging for Evaluating Postoperative Recurrence in Crohn's Disease.

Background & Aims: Colonoscopy is recommended to monitor for Crohn's disease (CD) recurrence after surgical resection. However, repeated colonoscopy is invasive and resource-intensive. We conducted a systematic review and meta-analysis to evaluate the pooled diagnostic accuracy of noninvasive biomarkers and imaging measures for detecting endoscopic CD recurrence, as compared with colonoscopy.

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.

Definitions, diagnosis, and management of postoperative recurrence in Crohn's disease patients with permanent ileostomy-a systematic review and meta-analysis.

Background And Aims: Over 10% of patients with Crohn's disease require permanent ileostomy. We aimed to summarize the existing data on diagnosis, definitions of recurrence, and management of Crohn's disease patients with permanent ileostomy.

Methods: MEDLINE, Embase, and CENTRAL databases were searched from inception to February 6, 2024.

Comprehensive care of ulcerative colitis: new treatment strategies.

Introduction: Ulcerative colitis is a chronic inflammatory condition of the colon driven by aberrant immune activation. Although advanced medical therapies form the cornerstone of ulcerative colitis management, unmet needs include failure to induce and sustain remission in a substantial proportion of patients and in managing acute severe ulcerative colitis. We review new treatment strategies that might improve patient outcomes in the management of moderate-to-severe ulcerative colitis.

Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study.

Background: Ulcerative colitis (UC) is a chronic inflammatory condition requiring continuous treatment and monitoring. There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.

Aim: To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.

Infliximab and Adalimumab in the Treatment of Fistulizing Crohn's Disease: A Propensity Score-Matched Analysis From the Prospective Persistence Australian National IBD Cohort (PANIC4) Study.

Introduction: There are spare data on comparative medication efficacy in fistulizing Crohn's disease (FCD), particularly with immunomodulator cotherapy. Persistence is a unique way to assess real-world outcomes.

Methods: The persistence of all dispensed biological agents was analyzed from the Australian Pharmaceutical Benefits Scheme registry data 2005-2021 for FCD.

Optimizing 5-aminosalicylate for moderate ulcerative colitis: expert recommendations from the Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition.

The lack of clear definition and classification for "moderate ulcerative colitis (UC)" creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC.

The phageome of patients with ulcerative colitis treated with donor fecal microbiota reveals markers associated with disease remission.

Bacteriophages are influential within the human gut microbiota, yet they remain understudied relative to bacteria. This is a limitation of studies on fecal microbiota transplantation (FMT) where bacteriophages likely influence outcome. Here, using metagenomics, we profile phage populations - the phageome - in individuals recruited into two double-blind randomized trials of FMT in ulcerative colitis.

Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial.

Background: The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC.

Methods: In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1).

Refining microbial community metabolic models derived from metagenomics using reference-based taxonomic profiling.

Characterization of microbial community metabolic output is crucial to understanding their functions. Construction of genome-scale metabolic models from metagenome-assembled genomes (MAG) has enabled prediction of metabolite production by microbial communities, yet little is known about their accuracy. Here, we examined the performance of two approaches for metabolite prediction from metagenomes, one that is MAG-guided and another that is taxonomic reference-guided.