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. Regional disparities in health-care access contribute to these challenges, especially in low-income countries. Addressing these inequities is crucial for improving global IBD outcomes. Using a Delphi methodology, experts from clinical care, research, public health and advocacy (including patient representation) identified priorities across six domains (37 statements in total): epidemiology, care models, treatment strategies, education and awareness, patient and community engagement, and leadership to promote health equity. These priorities emphasize quantifying the burden of IBD, addressing health-care disparities, validating care models, exploring novel treatments, advancing education, engaging patients and advocating for health equity policies. The comprehensive approach seeks to optimize care models, promote patient engagement and ensure equitable access to health care. The identified priorities serve as a guide for both clinical and non-clinical researchers, and funders dedicated to IBD-related initiatives, fostering international collaboration to improve IBD management and reduce its impact globally.

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. AI can streamline multiple trial phases, from target identification and patient recruitment to data analysis and monitoring. By integrating multi-omics data, electronic health records, and imaging repositories, AI can uncover molecular targets and personalize trial strategies, ultimately expediting drug development. However, the adoption of AI in IBD clinical trials encounters significant challenges. These include technical barriers in data integration, ethical concerns regarding patient privacy, and regulatory issues related to AI validation standards. Additionally, AI models risk producing biased outcomes if training datasets lack diversity, potentially impacting underrepresented populations in clinical trials. Addressing these limitations requires standardized data formats, interdisciplinary collaboration, and robust ethical frameworks to ensure inclusivity and accuracy. Continued partnerships among clinicians, researchers, data scientists, and regulators will be essential to establish transparent, patient-centered AI frameworks. By overcoming these obstacles, AI has the potential to enhance the efficiency, equity, and efficacy of IBD clinical trials, ultimately benefiting patient care.

Growing evidence shows that ulcerative colitis (UC) is a progressive disease similar to Crohn’s disease (CD). The UC-related burden is often underestimated by physicians and a standard step-up therapeutic approach is preferred. However, in many patients with UC the disease activity is not adequately controlled by current management, leading to poor long-term prognosis. Data from both randomized controlled trials and real-world studies support early intervention in CD in order to prevent disease progression and irreversible bowel damage. Similarly, an early disease intervention during the so-called “window of opportunity” could lead to better outcomes in UC. Here, we summarize the literature evidence on early intervention in patients with UC, highlighting strengths and limitations of this approach.

Inflammatory bowel diseases (IBDs) are chronic and disabling conditions that, uncontrolled, lead to irreversible bowel damage and associated comorbidities. Despite the new era of biological therapies, IBDs remain not curative. The treatment purpose is to induce endoscopic remission, reduce the progression of the disease and improve the quality of life. Optimal and early treatment could enable the prevention of their complications. Small molecules, administrated as oral agents, have the capacity of overcoming the limitations of biologic agents (i.e., parenteral administration, rapidity of action and primary and secondary non-responsiveness). Of special interest are results from the use of oral sphingosine 1-phosphate (S1P) receptor modulators (ozanimod, etrasimod, fingolimod and laquinimod), based on S1P activities to target lymphocyte recirculation in the mucosa, acting as immunosuppressive agents. Most S1P modulators are reported to be safe and effective in the treatment of both UC and CD. High and satisfactory rates of clinical remission as well as endoscopic improvement and remission can be achieved with these molecules. Safety alarms remain rather low, although the S1P binding to two of its G protein-coupled receptors, 2 and 3 (S1PR2 and S1PR3), may be associated with cardiovascular risks. Cost-effectiveness studies and head-to-head trials are needed to better define their place in therapy. This review summarizes these emerging data published by PubMed and EMBASE databases and from ongoing clinical trials on the safety and efficacy of selectivity of S1P modulators in the treatment of IBD.

Fibro-stenosing Crohn’s disease (CD) is a common disease presentation that leads to impaired quality of life and often requires endoscopic treatments or surgery. From a pathobiology perspective, the conventional view that intestinal fibro-stenosis is an irreversible condition has been disproved. Currently, there are no existing imaging techniques that can accurately quantify the amount of fibrosis within a stricture, and managing patients is challenging, requiring a multidisciplinary team. Novel therapies targeting different molecular components of the fibrotic pathways are increasing regarding other diseases outside the gut. However, a large gap between clinical need and the lack of anti-fibrotic agents in CD remains. This paper reviews the current state of pathobiology behind fibro-stenosing CD, provides an updated diagnostic and therapeutic approach, and finally, focuses on clinical trial endpoints and possible targets of anti-fibrotic therapies.

Biologic agents and oral small molecules are the mainstays of inflammatory bowel disease [IBD] management. However, an unmet clinical need remains for additional agents with novel mechanism of action which are effective, safe, and disease-modifying; this is due to the substantial proportion of patients who do not respond, lose response, or develop intolerance to currently marketed products. microRNAs [miRNAs] that play a role in the modulation of signal transduction pathways implicated in the development of IBD hold the potential to be used as therapeutic targets. Recently, a novel first-in-class compound, obefazimod, originally conceived as a human immunodeficiency virus [HIV] infection drug, has shown great promise in phase II induction trials for ulcerative colitis [UC] patients. Findings from the maintenance phases of trials showed that long-term obefazimod treatment provides continued improvement in clinical symptoms of disease, with a substantial proportion of patients in clinical remission, and an overall good safety profile. With a novel mechanism of action, obefazimod is an orally available small molecule with anti-inflammatory properties through the specific and selective upregulation of miR-124 expression. The aim of this paper is to critically review the available evidence related to pharmacokinetics and pharmacodynamics, and to discuss the potential clinical implications of this first-in-class oral small molecule.