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.

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.

Reaching the therapeutic ceiling in IBD: Can Advanced Combination Treatment (ACT) offer a solution?

The term Advanced Combination Treatment (ACT) involves the combination of at least two biologics or the use of a biologic with a small molecule drug, each with different mechanisms of action. This narrative review evaluates the current evidence supporting ACT in inflammatory bowel disease (IBD), focusing on preclinical studies, real-world evidence, and randomized controlled trials. A systematic review of randomized controlled trials has concluded that ACT significantly improves clinical outcomes, without significant safety concerns in patient with IBD.

Comparative Safety of Janus Kinase Inhibitors vs Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases.

Background & Aims: We conducted a retrospective cohort study comparing the safety of Janus kinase (JAK) inhibitors vs tumor necrosis factor-a (TNF) antagonists in patients with inflammatory bowel diseases (IBDs).

Methods: Using an administrative claims database, we identified patients with IBD who were new users of either JAK inhibitors or TNF antagonists between 2016 and 2023 and had insurance coverage for at least 1 year before and after treatment initiation. We compared the risk of infections (overall and serious infections requiring hospitalization), venous thromboembolism (VTE), and major adverse cardiovascular events (MACE) through stabilized inverse probability of treatment weighted Cox proportional hazards model accounting for disease characteristics, health care utilization, comorbidities, prior and concomitant medications, and competing risk of mortality.

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.

Day 3 Oxford Criteria Predict Steroid non-response for Acute Severe Ulcerative Colitis in the Post Biologic Era.

Background And Aims: Outcomes of patients admitted with acute severe ulcerative colitis(ASUC) in the post biologic era are under explored, as well as ability of scoring indices to predict early steroid non-response.

Methods: This Retrospective cohort study included adults hospitalized with ASUC(2010-2022) at London Health Sciences Centre, Canada. Steroid response, need for rescue therapy, colectomy during index hospitalization and colectomy and hospitalization at 3- and 12-months following discharge was assessed.

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.

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.

The Effectiveness of Medical Therapies for Joint, Skin and Eye Extraintestinal Manifestations in IBD-An Umbrella Review.

Background: Extraintestinal manifestations (EIMs) occur commonly in patients with inflammatory bowel disease (IBD), affecting joints, skin, eyes and other organs, and contributing to morbidity and long-term disability.

Aims: To synthesise evidence from systematic reviews (SRs) on the effectiveness and safety of medical treatments for IBD EIMs in IBD of joints, skin and eyes.

Methods: For this umbrella review, we searched three databases for relevant SRs published until May 30, 2024.

Shaping the future of inflammatory bowel disease: a global research agenda for better management and public health response.

Inflammatory bowel disease (IBD) is a growing global health challenge affecting more than 7 million people worldwide. With increasing prevalence across all age groups, including children and adolescents, IBD places substantial strain on health-care systems and society, resulting in high direct medical costs, lost productivity and reduced quality of life. Despite therapeutic advances, suboptimal disease control and delays in timely diagnosis and adequate treatment persist.

5-Aminosalicylates for non-surgical patients with active or quiescent Crohn's disease: an overview of systematic reviews (umbrella review).

Background: 5-aminosalicylates (5-ASAs) are commonly used in non-surgical patients with Crohn's disease (CD), especially in mild-to-moderate disease, despite current guidelines against their use. Despite this, the evidence regarding their efficacy is mixed, with conflicting findings in systematic reviews (SRs).

Aims: We conducted an overview of reviews (umbrella review) to consolidate existing knowledge from published SRs on using 5-ASAs in patients with active or quiescent CD.

Management of Patients with IBD and History of Cancer.

The use of advanced therapies, including biologics and small molecules, has become an established clinical practice for the treatment of moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). However, certain patient populations, such as those with a history of cancer, are often excluded from clinical trials evaluating the efficacy and safety of these therapies. This exclusion has historically left clinicians with limited evidence to guide treatment decisions in this high-risk group.

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.

Artificial intelligence to revolutionize IBD clinical trials: a comprehensive review.

Integrating artificial intelligence (AI) into clinical trials for inflammatory bowel disease (IBD) has potential to be transformative to the field. This article explores how AI-driven technologies, including machine learning (ML), natural language processing, and predictive analytics, have the potential to enhance important aspects of IBD trials-from patient recruitment and trial design to data analysis and personalized treatment strategies. As AI advances, it has potential to improve long-standing challenges in trial efficiency, accuracy, and personalization with the goal of accelerating the discovery of novel therapies and improve outcomes for people living with IBD.

TL1A Inhibition in Inflammatory Bowel Disease: A Pipeline Review.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), remains challenging to manage, with a substantial proportion of patients not responding to conventional therapies or developing complications. The tumor necrosis factor (TNF) superfamily member TL1A has emerged as an important player in the pathogenesis of IBD, influencing pathways of inflammation and fibrosis. This leading article reviews the role of TL1A in IBD, evaluates the efficacy of anti-TL1A therapies in clinical trials, and discusses future directions for research and treatment.

Differential Efficacy of Advanced Therapies in Inducing Remission in Ulcerative Colitis Based on Prior Exposure to TNF Antagonists.

Background And Aims: We sought to ascertain how prior exposure to tumor necrosis factor (TNF) antagonists impacts treatment response with various classes of advanced therapies in patients with ulcerative colitis (UC), through a systematic review and meta-analysis.

Methods: Through a systematic review of multiple databases through June 30, 2024, we identified 17 randomized controlled trials in 8871 adults with moderate-severe UC who were treated with different advanced therapies vs placebo, and reported efficacy in induction of clinical remission, stratified by prior exposure to TNF antagonists. We calculated the ratio of odds ratio of achieving remission with active drug vs placebo, in TNF antagonist-naïve vs TNF antagonist-exposed patients.

Effectiveness of Ustekinumab for Patients With Moderate-to-Severe Ulcerative Colitis: A Multicenter Real-World Canadian Study.

Introduction: We aimed to evaluate the real-world effectiveness and safety of ustekinumab for the treatment of both bio-naive and bio-exposed ulcerative colitis patients in a real-world setting.

Methods: Retrospective, Canadian multicenter cohort study. Primary outcomes were clinical remission and endoscopic remission.

Heterogeneity of definition of upper gastrointestinal tract in different guidelines of Crohn's disease: A scoping review.

Crohn's Disease (CD) can affect any part of the gastrointestinal (GI) tract, including the upper GI tract (UGIT). However, the definitions and classifications of upper GI CD (UGICD) vary. We conducted a scoping review to explore how UGIT and UGICD are defined and to assess the heterogeneity of these definitions in published CD guidelines, aiming to inform future initiatives for harmonizing definitions.

Efficacy and safety of Advanced Combination Treatment in immune-mediated inflammatory disease: A systematic review and meta-analysis of randomized controlled trials.

Objectives: Advanced combination treatment (ACT), defined as a combination of at least 2 biologic agents, a biologic agent and an oral small molecule, 2 oral small molecules drug with different mechanisms of action is a proposed strategy to improve outcomes in patients with immune-mediated inflammatory disease (IMID). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ACT with monotherapy in patients with select IMIDs.

Methods: Through a systematic literature search, we identified 10 RCTs (n = 1154) comparing ACT with single agent therapy (monotherapy).