Dignass, Axel

Abstract Background & Aims Central reading of endoscopy and histopathology is the current standard for disease activity assessment in inflammatory bowel disease (IBD) clinical trials but is limited by interreader and intrareader variability, operational delays, and cost. Artificial intelligence (AI) and machine learning (ML) offer the potential to improve accuracy, efficiency, and reproducibility. The International Organization for the Study of IBD (IOIBD) developed consensus statements on AI/ML use for endoscopic and histologic endpoint assessment in IBD trials. Methods As part of the IOIBD endpoints cluster initiative, a narrative, evidence-informed review with literature searches of Medline and Embase (January 2018-February 2025) identified studies applying AI/ML to endoscopy or histology in IBD. Relevant evidence informed 36 survey statements formulated by a steering committee. Seventy-two IOIBD members were invited to vote online; consensus required ≥80% agreement (score: 7-10 on a 10-point scale). Results Forty-five members completed the survey. Consensus was reached for 28 statements related to endoscopy, pathology, and trial design. Experts agreed that AI-based central reading could improve diagnostic accuracy, expedite processes, reduce costs, and enhance reproducibility. Combining human and AI assessments was favored over AI replacement. The key limitations identified included insufficient validation, generalizability concerns, and dependence on human-annotated training datasets. Conclusions This IOIBD consensus supports the integration of AI/ML into central reading for IBD clinical trials to improve objectivity, efficiency, and consistency, while maintaining human oversight. Further research should address validation, regulatory frameworks, and multimodal integration to enable broader adoption in both trials and clinical practice.

Abstract Background and Aims Intestinal ultrasound (IUS) is increasingly used to monitor treatment efficacy in inflammatory bowel disease (IBD) trials. However, standardized definitions for response, remission, and optimal assessment timing remain undefined. An international expert consensus meeting was held to establish IUS endpoints for clinical trials. Methods A panel of 35 international gastroenterologists and radiologists participated in a modified Delphi process, reviewing the literature and developing consensus statements. Agreement was defined as at least 75% consensus. Results Consensus was reached on 150 statements across four domains: general IBD (30 statements), luminal Crohn’s disease (CD) (43), perianal CD (51), and ulcerative colitis (UC) (26). For luminal CD and UC, ultrasound response was defined by: (1) a ≥25% reduction in bowel wall thickness (BWT) from baseline, or (2) multifactorial improvement, combining BWT reduction with ≥1 grade decrease in color Doppler signal (CDS) or another IUS parameter. Assessments were set at weeks 4-8 for the colon and week 12 for the terminal ileum. Ultrasound remission in luminal CD was defined as: (1) BWT normalization (≤3 mm) or (2) normalization of multiple parameters, including BWT, CDS, and all other IUS parameters. Similar remission criteria were proposed for UC, but the sigmoid BWT normal range (3-4 mm) remained uncertain. The bowel ultrasound score (BUSS) for CD and the Milan ultrasound criteria (MUC) for UC were supported as standardized scoring systems for trials. Conclusion This consensus provides standardized IUS definitions to enhance consistency in IBD trials, supporting the integration of IUS in future research.

Abstract 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. Randomized controlled trials, cohort and cross-sectional studies, and case series of more than 5 patients reporting on postoperative recurrence or the need for surgery in patients with Crohn’s disease and permanent ileostomy were included. Search results were independently screened, and full text of all titles meeting eligibility criteria was obtained. Outcomes of interest included diagnostic techniques, recurrence definitions, and management approaches. We estimated pooled rates (with 95% confidence interval [CI]) of recurrence. Results Thirty cohort studies including 2055 Crohn’s patients with permanent ileostomy were included (53% female, median age at the time of ileostomy creation 32 years, the most common reason for ileostomy was refractory disease). The postoperative recurrence rate was 27% (95% CI, 21.3–33.3, 26 studies, 451/1805 patients). Modalities for diagnosis of Crohn’s disease recurrence were symptoms (15 studies), endoscopy (4 studies), histology from endoscopic biopsies (2 studies), imaging (5 studies), and surgery (22 studies). The reported definitions of recurrence for each modality were heterogeneous. Conclusions There is a lack of standardized monitoring tools and criteria for diagnosing recurrence in patients with Crohn’s disease and permanent ileostomy. The results of this systematic review will form the basis of a global expert recommendation exercise focused on developing management standards and trial endpoints for this condition.

INTRODUCTION: Patients with ulcerative colitis (UC) and prior biologic failure may have reduced or delayed efficacy with subsequent advanced therapies. This analysis evaluated the efficacy and safety of ozanimod during the True North (TN) study and its open-label extension (OLE) in biologic-exposed patients with UC. METHODS: TN was a randomized, placebo-controlled 52-week trial (10-week induction, 42-week maintenance period). Eligible patients could enter the OLE. Clinical outcomes were assessed at TN week (W) 10 and W52 and OLE W46 and W94. Symptomatic efficacy was evaluated through induction and in the OLE until W94. Safety was assessed. RESULTS: This analysis included 376 biologic-exposed patients. In the placebo-controlled cohort, more ozanimod-treated patients achieved clinical response than placebo at W10 regardless of the number or type of prior biologics; patients who used 1 vs ≥2 prior biologics achieved higher efficacy rates. Efficacy rates were higher at W52 than W10 and were similar across subgroups regardless of the number or type of prior biologics. Significantly greater proportions of ozanimod vs placebo patients achieved symptomatic response by W5 ( P = 0.0173) and symptomatic remission by W10 ( P = 0.0207). Among biologic-exposed TN W10 ozanimod nonresponders who entered the OLE, 61% achieved symptomatic response with an extra 10 weeks of ozanimod treatment. Ozanimod efficacy was durable for ∼3 years of continuous treatment in biologic-exposed W52 clinical responders who entered the OLE. No new safety signals were observed. DISCUSSION: Ozanimod was effective and safe in biologic-exposed patients with UC, but these patients may require more time to respond to treatment. Clinical trial registry website and trial numbers: ClinicalTrials.gov, numbers NCT02435992 and NCT02531126.

Background: Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD). Methods: MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model. Results: Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: −0.07 −0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05–0.35, p<0.01). 31.2% (95% CI: 23.8–39.7) of patients with IBD achieved endoscopic response, and there was a significant improvement in ulcerative colitis response score (SMD: −0.6,95% CI: −0.88 to 0.36, p<0.01). Furthermore, 17.6% (95% CI: 13.0–23.5) of patients experienced adverse events severe enough to discontinue therapy, and 29.9% (95% CI: 25.2–34.8) had a loss of response to biologics. Conclusions: Treatment of patients with PSC-IBD with biologics (vedolizumab, infliximab, and adalimumab) was not associated with improvement of biochemical markers of cholestasis. Biologics are effective in treating the colitis associated with PSC. Vedolizumab was associated with worsening liver enzymes in contrast to other biologics, a finding that warrants further study.

AbstractThe available COVID‐19 literature has focused on specific disease manifestations, infection control, and delivery or prioritization of services for specific patient groups in the setting of the acute COVID‐19 pandemic. Local health systems aim to contain the COVID‐19 pandemic and hospitals and health‐care providers rush to provide the capacity for a surge of COVID‐19 patients. However, the short, medium‐term, and long‐term outcomes of patients with gastrointestinal (GI) diseases without COVID‐19 will be affected by the ability to develop locally adapted strategies to meet their service needs in the COVID‐19 setting. To mitigate risks for patients with GI diseases, it is useful to differentiate three phases: (i) the acute phase, (ii) the adaptation phase, and (iii) the consolidation phase. During the acute phase, service delivery for patients with GI disease will be curtailed to meet competing health‐care needs of COVID‐19 patients. During the adaptation phase, GI services are calibrated towards a “new normal,” and the consolidation phase is characterized by rapid introduction and ongoing refinement of services. Proactive planning with engagement of relevant stakeholders including consumer representatives is required to be prepared for a variety of scenarios that are dictated by thus far undefined long‐term economic and societal impacts of the pandemic. Because substantial changes to the delivery of services are likely to occur, it is important that these changes are embedded into quality and research frameworks to ensure that data are generated that support evidence‐based decision‐making during the adaptation and consolidation phases.