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.

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.

Is Transmural Healing an Achievable Goal in Inflammatory Bowel Disease?

: In the era of treat-to-target strategies in inflammatory bowel disease (IBD), transmural healing (TH) is gaining recognition as a promising therapeutic goal. TH has been associated with significantly better long-term outcomes, including reduced rates of hospitalization, surgery, and the need for therapy escalation. Cross-sectional imaging techniques, such as intestinal ultrasound (IUS), magnetic resonance imaging (MRI), and computed tomography enterography (CTE), offer a comprehensive, non-invasive means to assess this deeper level of healing.

Comparing standard versus intensified pneumococcal vaccination regimens in patients with inflammatory bowel disease on biologics: a prospective, multicenter, randomized, open-label study.

Background And Aims: Pneumococcal vaccination is essential for patients with inflammatory bowel diseases (IBD), but its efficacy is reduced in those on antitumor necrosis factor (TNF) or immunosuppressive therapy. This study compared immune responses to standard versus intensified pneumococcal vaccination strategies in IBD patients receiving anti-TNF (±immunosuppressors) or vedolizumab.

Methods: In a prospective, multicenter, randomized open-label study across 7 French university hospitals, IBD patients in clinical remission on biologic therapy (anti-TNF ± immunosuppressors, or vedolizumab) were randomized 1:1 to an intensified (PCV13/PCV13/PPSV23) or standard (PCV13/PPSV23) regimen.

Impact of Type 2 Diabetes on Clinical Outcomes and Advanced Therapy Use in Patients with Crohn's Disease: a Real-World Propensity Score-Matched Analysis.

Background: Type 2 diabetes mellitus (T2DM) may adversely affect the course and treatment outcomes of Crohn's disease (CD). However, data remain inconsistent.

Aims: To evaluate the impact of T2DM on clinical outcomes and advanced therapy use in patients with CD using real-world electronic health record data.

Bayesian Statistics: A Narrative Review on Application in Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBD) are highly heterogeneous conditions, varying in clinical manifestations, disease localization, progression, and response to treatment. Failing to account for this heterogeneity can substantially diminish the power of clinical trials and reduce the likelihood of detecting a true effect. In this review, we explore the transformative potential of Bayesian statistics in IBD clinical research, highlighting its ability to provide deeper insights, refine trial design, and facilitate more informed medical decision-making.

Longitudinal Profiles of Fecal Calprotectin and C-Reactive Protein in Relation to Outcomes in Crohn's Disease Patients on Infliximab.

Background And Aims: This study explored the relationship between fecal calprotectin (FCAL) and C-reactive protein (CRP) trajectory classes and composite outcomes (COs) in Crohn's Disease (CD) patients under infliximab (IFX). COs reflected disease progression, including surgery, hospitalizations, new fistulas, abscesses, strictures, and treatment escalation.

Methods: The DIRECT study was a multicenter, prospective investigation (2016-2019), including moderate-severe CD patients on IFX.

Treatment sequencing in inflammatory bowel disease: Towards clinical precision medicine.

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, raise ongoing challenges in clinical management due to their variable courses and impact on patient quality of life. The emergence of advanced therapies, from biologics to small molecules, has prompted the need for effective sequencing strategies to optimize patient outcomes. To this date, there is no algorithm for treatment sequencing and physicians must select the safest and most effective treatment according to each individual patient.

Biobetters and biosimilars in inflammatory bowel disease.

Biological therapies have revolutionized the management of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Among these, biosimilars and biobetters represent a growing area of therapeutic development. Biosimilars are nearly identical copies of original biologic drugs (reference products) with comparable safety, efficacy, and quality, but they offer the advantage of reduced costs and broader access.

Treatment targets in IBD: is it time for new strategies?

Inflammatory bowel diseases' traditional management focused primarily on symptom control, often failing to prevent long-term complications such as disease progression, disabilities, hospitalizations and surgeries. The introduction of biologics and small molecules has revolutionized IBD management, enhancing inflammation control. A pivotal advance in this field is represented by the Treat-to-Target approach, which prioritizes the achievement of specific goals like endoscopic remission and biomarker normalization, thus moving beyond symptomatic relief.

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.

Comparative effectiveness of tofacitinib versus upadacitinib for the treatment of acute severe ulcerative colitis.

Background & Aims: Tofacitinib and upadacitinib are Janus kinase (JAK) inhibitors that are increasingly used for the treatment of acute severe ulcerative colitis (ASUC). However, comparative analyses of safety and effectiveness have not been performed for their use in this setting.

Methods: This multicenter, retrospective study enrolled hospitalized adult patients treated with tofacitinib or upadacitinib for ASUC between January 2019 and June 2024.

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.

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.

Spatiotemporal analysis of Crohn's disease reveals PECAM2 signaling at the basis of inflammation-to-fibrosis transition.

Background And Aims: Crohn's disease is a chronic inflammatory disease of the bowel, often complicated by fibrotic strictures, for which medical treatment is lacking, and surgery is commonly required. The mechanisms underlying the progression from chronic inflammation to fibrosis are not yet defined. We aim to unravel Crohn's disease pathogenesis using a cutting-edge computational pipeline combining several available tools.

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.

The Role of Vitamin D in Inflammatory Bowel Diseases: From Deficiency to Targeted Therapeutics and Precise Nutrition Strategies.

Background: Vitamin D plays a crucial role in immune modulation, gut barrier integrity, and inflammation regulation, making it highly relevant in inflammatory bowel disease (IBD). IBD patients often exhibit vitamin D deficiency, which has been linked to increased disease activity, impaired mucosal healing, and a higher risk of complications, including infections and osteoporosis.

Methods: This review examines the biological functions of vitamin D in maintaining intestinal homeostasis, particularly in the context of IBD.

The preclinical discovery and development of upadacitinib for the treatment of Crohn's disease.

Introduction: The JAK-STAT pathway plays a pivotal role in immune regulation and is implicated in the pathogenesis of Crohn's disease (CD). Upadacitinib is a JAK inhibitor with greater selectivity for JAK1 over JAK2 and JAK3, and is emerging as a promising alternative to biologic therapies in CD.

Areas Covered: A literature search of MEDLINE and EMBASE up to February 2025 was conducted using defined keywords to identify preclinical, clinical, and real-world studies on upadacitinib in CD.

JAK Inhibitors and Risk of Cancer in IBD Patients.

Janus kinase inhibitors, including tofacitinib, filgotinib, and upadacitinib, have emerged as effective therapeutic options for the management of inflammatory bowel diseases (IBDs). By targeting the JAK-STAT signaling pathway, these agents modulate immune responses and reduce inflammation. However, concerns regarding the potential risk of malignancy associated with their use have gained significant attention.

Janus Kinase (JAK) Inhibitor-Induced Acne in Inflammatory Bowel Disease: An International, Multicenter, Retrospective Cohort Study.

Background & Aims: JAK inhibitor-associated acne is a common but poorly understood adverse event. This study aimed to investigate the epidemiology, clinical characteristics, and treatment outcomes of this condition in patients with inflammatory bowel disease (IBD).

Methods: This international, multicenter, retrospective cohort study consecutively enrolled JAK-inhibitor-treated patients with IBD who subsequently developed acne.

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.

Positioning Guselkumab in The Treatment Algorithm of Patients with Crohn's Disease.

Guselkumab, a selective interleukin-23 (IL-23) inhibitor, has emerged as a promising biologic therapy for the management of patients with moderate-to-severe Crohn's disease (CD) and has been recently approved for its treatment. Unlike conventional therapies, guselkumab offers a different mechanism of action by selectively inhibiting IL-23, a key cytokine implicated in the pathogenesis of CD. IL-23 drives intestinal inflammation through activation of the Th17 cell pathway and other immune processes, positioning IL-23 inhibition as a critical therapeutic approach.