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.

Etrasimod for the symptomatic relief of ulcerative colitis: a post-hoc analysis from the ELEVATE UC clinical programme.

Objective: Bothersome ulcerative colitis (UC) symptoms include stool frequency (SF), rectal bleeding (RB), abdominal pain and bowel urgency; symptomatic relief is a key treatment goal. Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate receptor modulator for the treatment of moderately to severely active UC. We assessed outcomes related to symptomatic relief among patients with moderately to severely active UC in the phase III ELEVATE UC clinical programme.

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.

Systematic Review With Meta-Analysis: Safety and Effectiveness of Combining Biologics and Small Molecules in Inflammatory Bowel Diseases.

Background: The systematic review and meta-analysis (SRMA) evaluates the safety and effectiveness of combining biologics and/or small molecules in treating refractory inflammatory bowel diseases (IBD).

Methods: Our 2022 SRMA identified 13 studies published until November 3, 2020. An updated systematic search was completed from May 2020 through January 31, 2024.

A Phase 2 Study of MORF-057, an Oral α4β7 Integrin Inhibitor in Moderately to Severely Active Ulcerative Colitis.

Background & Aims: MORF-057 is an orally administered small-molecule drug that inhibits α4β7 integrin-mediated recruitment of α4β7-expressing lymphocytes to the gut, a process implicated in the pathology of ulcerative colitis (UC). This study evaluated the efficacy, pharmacokinetics, pharmacodynamics, safety, and tolerability of MORF-057 in participants with moderately to severely active UC.

Methods: This open-label, phase 2a, single-arm, multicenter trial comprised a 6-week screening period, a 52-week active treatment period (including a 12-week induction period and 40-week maintenance period), and a 4-week safety follow-up period.

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.

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.

Efficacy and Safety of Infliximab and Vedolizumab Maintenance Therapy in Patients with Crohn's Disease and Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Direct comparative data for infliximab and vedolizumab are limited due to lack of head-to-head trials. This systematic review and meta-analysis compared the efficacy and safety of infliximab and vedolizumab as intravenous or subcutaneous maintenance treatments for adults with moderately to severely active Crohn's disease or ulcerative colitis. Medical databases, PubMed, Embase, and the Cochrane Library were systematically searched from January 2010 to May 2024 to identify Phase 1 to 3 randomized controlled trials.

Efficacy of Etrasimod in Ulcerative Colitis: Analysis of ELEVATE UC 52 and ELEVATE UC 12 by Baseline Endoscopic Severity.

Background & Aims: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately to severely active ulcerative colitis. In this post hoc analysis, induction and maintenance efficacy of etrasimod 2 mg versus placebo were assessed by baseline Mayo endoscopic subscore in ELEVATE UC 52 and ELEVATE UC 12.

Methods: Moderate and severe endoscopic disease were defined as a centrally read endoscopic subscore of 2 and 3, respectively.

Bowel urgency in ulcerative colitis: effect of baseline urgency and change in urgency in response to mirikizumab.

Background: Mirikizumab has demonstrated efficacy in moderately to severely active ulcerative colitis. A 1-2-point change in Urgency Numeric Rating Scale (NRS) score can be meaningful for patients. In these post-hoc analyses, we evaluated the efficacy of mirikizumab compared to placebo by baseline Urgency NRS score groups (0-3, 4-6, and 7-10) and its effect on bowel urgency severity over time.

Wearable Devices Identify Altered Sleep Characteristics and Sleep Trajectories in Active Inflammatory Bowel Disease.

Background And Aims: Poor sleep is associated with flares of inflammatory bowel disease (IBD). Studies often rely on subjective assessments of sleep and disease activity. Our aim is to use wearable devices to objectively assess the impact of inflammation and symptoms on sleep architecture in IBD.

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.

Safety and efficacy of the anti-TL1A monoclonal antibody tulisokibart for Crohn's disease: a phase 2a induction trial.

Background: TNF-like cytokine 1A (TL1A) is a key mediator of inflammation and fibrosis. The efficacy and safety of the anti-TL1A monoclonal antibody tulisokibart as induction treatment was assessed in adults with moderately to severely active Crohn's disease with a history of insufficient response, loss of response, or intolerance to conventional or approved biological therapies.

Methods: In the phase 2a, multicentre, open-label APOLLO-CD study, participants aged 18 years or older with moderately to severely active Crohn's disease, as defined by a Crohn's Disease Activity Index (CDAI) of 220-450 and a Simple Endoscopy Score for Crohn's Disease (SES-CD) of at least 6 for ileocolonic or colonic disease or at least 4 for isolated ileal disease, received intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10).

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.

Obefazimod in patients with moderate-to-severely active ulcerative colitis: efficacy and safety analysis from the 96-week open-label maintenance phase 2b study.

Background And Aims: Obefazimod is an oral small molecule that selectively enhances the expression of a single micro-RNA (miRNA), miR-124. Obefazimod has demonstrated safety and efficacy in patients with moderate-to-severely active ulcerative colitis (UC) in a phase 2b induction trial. This analysis presents the 2-year outcome data of the open-label maintenance (OLM) study.

Distinct perturbances in metabolic pathways associate with disease progression in inflammatory bowel disease.

Background And Aims: Patients with inflammatory bowel disease (IBD) exhibit distinct shifts in circulating metabolite levels linked to disease activity and phenotype, but associations with disease progression remain unexplored. Our aim was to investigate relationships between circulating metabolites and metabolic pathways with disease progression risk in patients with IBD.

Methods: We performed an observational cohort study using the Mount Sinai Crohn's and Colitis Registry.

Comparing Outcomes With Subcutaneous Infliximab (CT-P13 SC) by Baseline Immunosuppressant Use: A Post Hoc Analysis of the LIBERTY-CD and LIBERTY-UC Studies.

Background: Superior efficacy of subcutaneous infliximab (CT-P13 SC) over placebo for maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC) was demonstrated in the randomized LIBERTY-CD and LIBERTY-UC studies. The current post hoc analysis compared outcomes with CT-P13 SC by baseline immunosuppressant use.

Methods: Patients with moderately to severely active CD or UC randomized to the CT-P13 SC maintenance arm of the 54-week LIBERTY trials at week 10 and who were treated in the open-label extension (weeks 56-102) were included.

Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn's disease and ulcerative colitis: 2-year results from open-label extensions of two randomized controlled trials (LIBERTY).

Background And Aims: In the LIBERTY phase 3 studies in Crohn's disease (CD) or ulcerative colitis (UC), maintenance CT-P13 subcutaneous (SC) 120 mg was more effective than placebo after 1 year. Here we report 2-year data from the LIBERTY open-label extensions.

Methods: Two randomized, placebo-controlled, double-blind studies evaluated the efficacy and safety of CT-P13 SC maintenance in moderate-to-severe CD or UC.

Efficacy and Safety of Guselkumab Subcutaneous Induction and Maintenance in Participants With Moderately to Severely Active Crohn's Disease: Results From the Phase 3 GRAVITI Study.

Background & Aims: Subcutaneous (SC) induction and maintenance with guselkumab was evaluated in adult participants with moderately to severely active Crohn's disease.

Methods: The Phase 3 double-blind, placebo-controlled, treat-through GRAVITI study randomized 347 participants 1:1:1 to guselkumab 400 mg SC every 4 weeks→100 mg SC every 8 weeks (n = 115), guselkumab 400 mg SC every 4 weeks→200 mg SC every 4 weeks (n = 115), or placebo (n = 117). Placebo participants meeting rescue criteria received guselkumab from week 16 onward.

Efficacy and Safety of Etrasimod in Patients With Moderately to Severely Active Ulcerative Colitis Stratified by Baseline Modified Mayo Score: A Post Hoc Analysis From the Phase 3 ELEVATE UC Clinical Program.

Background: Etrasimod is an oral, once daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). This post hoc analysis of the ELEVATE UC clinical program describes etrasimod efficacy and safety by patients' baseline disease activity.

Methods: Predefined efficacy endpoints were assessed at week 12 in patients with moderately (modified Mayo score [MMS] 5-7) or severely (MMS 8-9) active UC using pooled data from ELEVATE UC 52 and ELEVATE UC 12.

Physiological Data Collected From Wearable Devices Identify and Predict Inflammatory Bowel Disease Flares.

Background & Aims: Wearable devices capture physiological signals noninvasively and passively. Many of these parameters have been linked to inflammatory bowel disease (IBD) activity. We evaluated the associative ability of several physiological metrics with IBD flares and how they change before the development of flare.