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Paediatric ulcerative colitis 2025 guideline

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Paediatric ulcerative colitis 2025 guideline

Patrick Van Rheenen 1

Affiliations

1 University Medical Center Groningen, Groningen, Netherlands

Summary

AI Generated

Updated paediatric ulcerative colitis guidelines recommend higher-dose infliximab with proactive therapeutic drug monitoring and provide structured pathways for ambulatory and acute severe disease management.

The speaker stated that infliximab is now recommended at 10 mg/kg per dose at weeks 0, 2, and 6, then every 4 to 8 weeks for maintenance in ambulatory UC, representing a change from 2018 guidelines.
In uncomplicated UC, therapeutic drug monitoring should be performed before the fourth infliximab infusion at week 14 with a target trough level of 8 mg/L or above, while patients with increased clearance risk factors should have TDM at week 6 targeting 50 mg/L or above.
For acute severe colitis with Pucai score over 65, the speaker stated that second-line infliximab should be initiated on day 5 of intravenous corticosteroids at 10 mg/kg at weeks 0, 1, and 3, then every 2 to 3 weeks.
Approximately 80 percent of children with UC present with pancolitis, making disease more extensive than in adults, according to the speaker.
The speaker noted that approximately two-thirds of the guideline statements are based on expert consensus rather than high-level evidence, reflecting limited paediatric-specific trial data.
Alternative biologics and small molecules are mentioned as options after anti-TNF failure but most have not been formally approved for paediatric use, with approval lag times of 6 to 11 years after adult licensing.

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Abstract

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine Paediatrics Surgery

Session

What's new in ulcerative colitis 2025?

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Best of UEG Week - IBD with Bel Kok

Bel Klaartje Kok, Pradeep Mundre

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Abstract

Topics

IBD

Published

2025

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... for medical therapy in inflammatory bowel diseases

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... for medical therapy in inflammatory bowel diseases

Chris Lamb 1

Affiliations

1 Newcastle Hospitals NHS Foundation Trust, Newcastle, United Kingdom

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Abstract

Event

UEG Week Berlin 2025

Topics

Colorectal IBD Surgery

Session

Predicting patient outcomes...

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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DISENTANGLING THE ASSOCIATION BETWEEN INFLAMMATORY BOWEL DISEASE AND OTHER IMMUNE-MEDIATED DISEASES: LEVERAGING GENEALOGICAL, GENETIC, AND MICROBIAL PROFILES ACROSS A HARMONIZED POPULATION FRAMEWORK

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DISENTANGLING THE ASSOCIATION BETWEEN INFLAMMATORY BOWEL DISEASE AND OTHER IMMUNE-MEDIATED DISEASES: LEVERAGING GENEALOGICAL, GENETIC, AND MICROBIAL PROFILES ACROSS A HARMONIZED POPULATION FRAMEWORK

Marie Vestergaard 1, Alonzo Alfaro-Núñez 2, Aleksejs Sazonovs 1, Georgios Athanasiadis 3, Tine Jess 4

Affiliations

1 PREDICT, Dep. Of Clinical Medicine, AAU, Copenhagen Sv, Denmark

2 PREDICT, Dep. Of Clinical Medicine, AAU, Copenhagen Sv, Denmark|||Department of Clinical Biochemistry, Naestved Hospital, Naestved, Denmark

3 Department of Evolutionary Biology, Ecology and Environmental Sciences, Barcelona University, Barcelona, Spain

4 PREDICT, Dep. Of Clinical Medicine, AAU, Copenhagen Sv, Denmark|||Aalborg University Hospital, Aalborg, Denmark

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Abstract

Introduction

Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is part of a broader spectrum of immune-mediated inflammatory diseases (IMIDs). Clinical and epidemiological studies indicate a higher prevalence of IMIDs among patients with IBD and their first-degree relatives, with a significant proportion of patients with IBD also diagnosed with conditions such as asthma, psoriasis, and rheumatoid arthritis^1,2. These patterns suggest shared genetic and/or environmental risk factors. The clinical intersections call for a multidisciplinary management strategy in which decisions account for the broader immune landscape rather than focusing on each diagnosis in isolation^1,3.

Aims & Methods

This study aimed to characterize the relationship between IBD and other IMIDs and disentangle genetic and environmental contributions. This was done by analyzing the tetrachoric correlation⁴ between disease codes registered for 107,651 full sibling pairs born between 1910 and 2010 in the Danish nationwide health registries. We then estimated SNP-based correlations based on summary statistics from genome-wide association studies of each disease using LDSC⁵. Lastly, we downloaded and reanalyzed all V3-V4 16S rDNA fecal microbiota samples available from NCBI⁶ in a unified bioinformatical pipeline. We used this data to generate microbiota disease profiles and estimate their correlations across IBD and IMIDs.

Results

We show that CD and UC have distinct patterns of correlations with other IMIDs. Asthma and celiac disease were correlated with CD (asthma: ρ=0.12, 95% CI=0.10-0.13, celiac disease: ρ=0.12, 95% CI=0.08-0.17), but not UC within full siblings. Oppositely, sarcoidosis (ρ=0.16, 95% CI=0.13-0.19), multiple sclerosis (ρ=0.09, 95% CI=0.06-0.12), systemic lupus erythematosus (SLE) (ρ=0.19, 95% CI=0.13-0.25), and Sjögren’s syndrome (ρ=0.15, 95% CI=0.10-0.20) correlated with UC but not CD. The IMIDs Graves’ disease, type 1 diabetes, iridocyclitis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis correlated with both CD and UC. Evaluating genetic and gut microbial correlations highlighted that UC exhibits microbiota-linked correlations with multiple sclerosis (ρ=0.11, 95% CI=0.01-0.21) and SLE (ρ=0.15, 95% CI=0.05-0.24) despite an estimated negative genetic overlap (multiple sclerosis: ρ=-0.18, 95% CI=-0.32--0.04, SLE: ρ=-0.21, 95% CI=-0.32--0.09), suggesting a key role for environmental factors, including microbial. In contrast, for both IBD subtypes rheumatoid arthritis showed consistent genetic (CD: ρ=0.12, 95% CI=0.02-0.21, UC: ρ=0.17, 95% CI=0.08-0.27) as well as microbial convergence (CD: ρ=0.30, 95% CI=0.20-0.38, UC: ρ=0.12, 95% CI=0.02-0.22), whereas the correlation with psoriasis appeared to be mainly genetically driven (CD SNP correlation: ρ=0.23, 95% CI=0.14-0.33, CD microbiota correlation: ρ=-0.13, 95% CI=-0.23--0.03, UC SNP correlation: ρ=0.25, 95% CI=0.15-0.35, UC microbiota correlation: ρ=0.06, 95% CI=-0.04-0.16).

Conclusion

These findings uncover heterogeneity in shared etiological pathways across immune diseases, underscoring the need for stratified approaches to diagnosis and therapeutic intervention in IBD. Importantly, our findings demonstrate that CD and UC—though often co-studied—harbor distinct immunogenetic and microbial associations, reinforcing the need for subtype-specific approaches in clinical management and research design. Further, the correlation between IBD and other IMIDs appears to be driven by different genetic and environmental mechanisms, which must be further explored.

References

1. Bezzio C, Corte C Della, Vernero M, et al. Inflammatory bowel disease and immune-mediated inflammatory diseases: looking at the less frequent associations. Therap Adv Gastroenterol 2022;15. Available at: https://journals.sagepub.com/doi/full/10.1177/17562848221115312 [Accessed March 14, 2025].
2. García MJ, Pascual M, Pozo C Del, et al. Impact of immune-mediated diseases in inflammatory bowel disease and implications in therapeutic approach. Sci Rep 2020;10:10731. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC7330038/ [Accessed March 14, 2025].
3. Park SW, Kim TJ, Lee JY, et al. Comorbid immune-mediated diseases in inflammatory bowel disease: a nation-wide population-based study. Aliment Pharmacol Ther 2019;49:165–172. Available at: https://pubmed.ncbi.nlm.nih.gov/30506945/ [Accessed March 14, 2025].
4. Falconer DS, Mackay TFC. Introduction to Quantitative Genetics. Third Ddit. Longman Scientific & Technical; 1989.
5. Bulik-Sullivan B, Finucane HK, Anttila V, et al. An atlas of genetic correlations across human diseases and traits. Nature Genetics 2015 47:11 2015;47:1236–1241. Available at: https://www.nature.com/articles/ng.3406 [Accessed March 14, 2025].
6. Sayers EW, Bolton EE, Brister JR, et al. Database resources of the national center for biotechnology information. Nucleic Acids Res 2022;50:D20–D26. Available at: https://pubmed.ncbi.nlm.nih.gov/34850941/ [Accessed March 14, 2025].

Disclosure

TJ reports consultancy for Ferring and Pfizer. The remaining authors have no disclosures.

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine Small Intestine & Nutrition Radiology & Imaging

Submission format

Abstract

Session

IBD: What about the environment?

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Francisca Joly

UEG Presentation

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

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How to fight fake news in medicine?

Wendi LeBrett 1

Affiliations

1 David Geffen School of Medicine, Los Angeles, United States of America

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Abstract

Event

UEG Week Berlin 2025

Topics

Immunology

Session

Opening Plenary

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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LINERIXIBAT SIGNIFICANTLY IMPROVES CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: RESULTS OF THE PIVOTAL PHASE 3 GLISTEN TRIAL

This content is part of Gutflix. Log in with your myUEG account, or create one free, to watch it.

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LINERIXIBAT SIGNIFICANTLY IMPROVES CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: RESULTS OF THE PIVOTAL PHASE 3 GLISTEN TRIAL

Gideon M. Hirschfield 1, Christopher L. Bowlus 2, David Jones 3, Andreas E. Kremer 4, Marlyn J. Mayo 5, Atsushi Tanaka 6, Pietro Andreone 7, Jidong Jia 8, Qinglong Jin 9, Ricardo Macias-Rodriguez 10, Alexander R. Cobitz 11, Brooke M. Currie 11, Ciara Gorey 12, Ivana Lazic 12, Danielle J. Podmore 12, Andrea Ribiero 13, Jennifer B. Shannon 14, Brandon Swift 14, Megan M. McLaughlin 11, Cynthia Levy 15

Affiliations

1 Toronto General Hospital, Toronto, Canada

2 University of California Davis School of Medicine, Sacramento, United States

3 Newcastle University, Newcastle Upon Tyne, United Kingdom

4 University Hospital Zurich, Zurich, Switzerland

5 University of Texas Southwestern Medical School, Dallas, United States

6 Teikyo University School of Medicine, Tokyo, Japan

7 Azienda Ospedaliero-Universitaria di Modena and Università di Modena e Reggio Emilia, Modena, Italy

8 Capital Medical University, Beijing, China

9 The First Hospital of Jilin University, Changchun, China

10 Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

11 GSK, Collegeville, United States

12 GSK, London, United Kingdom

13 GSK, Madrid, Spain

14 GSK, Durham, United States

15 University of Miami, Miami, United States

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Abstract

Introduction

Cholestatic pruritus is common, debilitating and undertreated in patients with primary biliary cholangitis (PBC). Here, we describe the results of GLISTEN (NCT04950127), a Phase 3 study investigating the efficacy and safety of the ileal bile acid transporter inhibitor linerixibat for pruritus in PBC.

Aims & Methods

In this double-blind, randomised, placebo-controlled study, patients with PBC and moderate-to-severe pruritus received oral linerixibat 40 mg or placebo twice daily. Pruritus severity and pruritus-related sleep interference were assessed using a 0–10 numerical rating scale. The primary endpoint was change from baseline in worst itch over 24 weeks. Secondary endpoints included: at Week 2, change in worst itch; over 24 weeks, change in sleep interference; at Week 24, proportion of responders (≥ 2-, ≥ 3-, ≥ 4-point reduction in worst itch) and analysis of responses to 2 patient global impression items (itch severity and change). Safety endpoints included adverse event (AE) reporting.

Results

238 patients were randomised; 95% were female, itch severity was mean (standard deviation [SD]) 7.34 (1.54), 52% had alkaline phosphatase < 1.67 times upper limit of normal, and 47% were receiving stable therapy for pruritus. Pruritus improvement over 24 weeks was significantly greater with linerixibat than placebo: least-squares (LS) mean change -2.86 versus -2.15, adjusted mean difference -0.72; p = 0.001. At Week 24, the observed mean (SD) difference from baseline in pruritus was -3.66 (2.50) with linerixibat and -2.82 (2.32) with placebo. The effect of linerixibat was rapid and superior to placebo at Week 2: LS mean change -1.78 versus -1.07, adjusted mean difference -0.71; p < 0.001. Linerixibat also significantly improved pruritus-related sleep interference over 24 weeks versus placebo: LS mean change ‑2.77 versus -2.24, adjusted mean difference -0.53; p = 0.024. At Week 24, more patients on linerixibat than placebo achieved a ≥ 2-point (68% vs 64%), ≥ 3-point (56% vs 43%) or ≥ 4-point (41% vs 29%) reduction in pruritus and a higher proportion of linerixibat than placebo-treated patients reported their pruritus was very much improved (55% vs 37%) or absent (21% vs 9%). AEs reported more frequently with linerixibat than placebo were predominantly gastrointestinal (GI), including diarrhoea (61% vs 18% of patients) and abdominal pain (18% vs 3% of patients); 4% of patients in the linerixibat group discontinued treatment due to diarrhoea.

Conclusion

In patients with PBC and moderate-to-severe pruritus, linerixibat rapidly and significantly improved pruritus and pruritus-related sleep interference versus placebo. While GI AEs were more common with linerixibat than placebo, they rarely led to treatment discontinuation.

Disclosure

Funded by GSK. Various authors declare conflicts of interest as consultants, employee, recipients of grants and stockholders. These will be reported in full during the presentation.

Event

UEG Week Berlin 2025

Topics

Hepatobiliary Immunology Mechanisms & Personalised Medicine

Submission format

Abstract

Session

Advances in management of immune-mediated biliary disease

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Nutritional management of small intestinal enteropathies

Francisca Joly 1

Affiliations

1 Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France

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Abstract

Event

UEG Week Berlin 2025

Topics

Immunology Small Intestine & Nutrition

Session

Coeliac or non-coeliac enteropathy?

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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