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Fistulising Crohn's disease: Underlying mechanism

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Fistulising Crohn's disease: Underlying mechanism

Judy Chou 1

1 Icahn School of Medicine at Mount Sinai, New York, United States of America

Event

UEG Week Berlin 2025

Topics

IBD Primary Care Surgery

Session

Disease primer: From inflammation to restoration - wound healing in IBD

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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The pregnant IBD patient (Complete Session)

Event

UEG Week Berlin 2025

Topics

IBD Paediatrics

Session

The pregnant IBD patient

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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How to boost your biology? Every day strategies to improve therapies and combinations

Britta Siegmund 1

1 Charité - Universitätsmedizin Berlin, Berlin, Germany

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine Surgery

Session

How to optimise success in IBD treatment

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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INFLAMMAGEING AND RISK OF DIGESTIVE SYSTEM DISEASES: A LARGE COHORT STUDY BASED ON THE UK BIOBANK

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Introduction

Chronic low-grade inflammation, known as inflammageing, has been implicated in the pathogenesis of various digestive diseases. However, large-scale systematic evaluations of the association between inflammageing biomarker profiles and digestive system disorders remain scarce. Understanding these associations may have important implications for early detection and intervention strategies.

Aims & Methods

Leveraging the multidimensional data from the UK Biobank, this study aimed to investigate the longitudinal relationships between circulating inflammatory markers and major digestive diseases. A total of 45,475 participants were included, with inflammageing levels calculated as the average of standardized values of four circulating inflammatory markers: TNF, IL1RN, IL18, and IL6.
Digestive disease outcomes were identified from hospital records (HES) and death registries, covering 25 major diagnoses, including gastroesophageal reflux disease (GERD), inflammatory bowel disease (IBD), and non-alcoholic fatty liver disease (NAFLD). Cox proportional hazards models were used to estimate hazard ratios (HRs), adjusting for age, sex, BMI, smoking, and other potential confounders.
In addition, Mendelian randomization (MR) analysis was conducted using GWAS data derived from inflammageing scores to evaluate potential causal effects on digestive outcomes. Mediation and subgroup analyses were performed to explore possible mediating factors.

Results

In the Cox regression analysis, 22 out of 25 digestive outcomes showed significant associations with baseline inflammageing levels (Bonferroni-corrected P < 0.05), with HRs ranging from 1.2 to 2.4.
Mediation analysis identified neutrophil counts and LDL-C as important mediators in these associations, suggesting potential biological pathways linking inflammageing to digestive disease development.

Conclusion

Elevated baseline inflammageing levels were significantly associated with a wide spectrum of digestive system diseases. The findings highlight a potential mechanistic role of systemic inflammation in digestive disease pathogenesis. The use of inflammageing-related biomarkers may aid in early identification of high-risk individuals, offering opportunities for early prevention and targeted interventions.

INFLAMMAGEING AND RISK OF DIGESTIVE SYSTEM DISEASES: A LARGE COHORT STUDY BASED ON THE UK BIOBANK

Weixiang Guan 1, Yan Qin 2, Yajie Zhang 3, Weihong Sha 3, Hao Chen 1

1 Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China, Guangzhou, China|||South China University of Technology, Guangzhou, China

2 The First Affiliated Hospital of Guangzhou Medical University, Guangzhouchi, China

3 Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China, Guangzhou, China

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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The management of postoperative Crohn’s disease

Eugeni Domenech Morral 1

1 Hospital Germans Trias i pujol, Badalona, Barcelona, Spain

Event

UEG Week Berlin 2025

Topics

Colorectal Endoscopy IBD Nurses

Session

Mistakes in…: Lower GI

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Poster

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Introduction

Guselkumab and risankizumab are monoclonal antibody treatments targeting interleukin 23 that are approved for the treatment of moderate to severely active ulcerative colitis (UC) in the United States. However, these agents have not been directly compared in a controlled setting.

Aims & Methods

A network meta-analysis (NMA) was conducted to compare guselkumab and risankizumab as maintenance therapy for UC, based on key outcomes from pivotal Phase 3 randomised controlled trials (RCTs). The COMMAND trial of risankizumab and the QUASAR trial of guselkumab were identified through systematic literature review. Frequentist, fixed-effect NMAs were conducted for key efficacy endpoints at the end of maintenance (52 weeks in COMMAND and 44 weeks in QUASAR) as reported by the trials: clinical remission, endoscopic improvement, endoscopic remission, and histologic endoscopic mucosal improvement (HEMI). Analyses included populations of variable advanced therapy (ADT) failure status (i.e., mixed). Data from these re-randomized RCTs were used directly, rather than normalising to mimic treat-through designs, given these trials are for same-class therapies and were similarly designed.

Results

NMAs found that guselkumab 200 mg every 4 weeks (Q4W) was significantly more efficacious than risankizumab 360 mg every 8 weeks (Q8W) on clinical remission (odds ratio [OR] 2.38; 95% confidence interval [CI] 1.25, 4.52) and endoscopic improvement (OR 2.26; 95% CI 1.21, 4.22). Guselkumab 200 mg Q4W had numerical benefits on endoscopic remission (OR 1.53; 95% CI 0.74, 3.16) and HEMI (OR 1.89; 95% CI 0.98, 3.63) compared with risankizumab 360 mg Q8W. Numerically higher benefits of guselkumab compared with risankizumab were also observed at lower doses (ie, guselkumab 100 mg Q8W and risankizumab 180 mg Q8W).

Conclusion

Results of this NMA suggest that guselkumab 200 mg Q4W is superior to risankizumab 360 mg Q8W for maintenance treatment of moderate to severely active UC on multiple efficacy endpoints including endoscopic improvement.

Table. Results summary for NMAs comparing guselkumab and risankizumab on clinical and endoscopic outcomes in UC.*

	Clinical remission		Endoscopic improvement		Endoscopic remission		HEMI
	GUS 100 mg Q8W	GUS 200 mg Q4W	GUS 100 mg Q8W	GUS 200 mg Q4W	GUS 100 mg Q8W	GUS 200 mg Q4W	GUS 100 mg Q8W	GUS 200 mg Q4W
RIS 180 mg Q8W	1.76 (0.92, 3.35)	2.13 (1.12, 4.06)^†	1.88 (1.00, 3.53)	2.04 (1.09, 3.83)^†	1.71 (0.82, 3.55)	1.64 (0.79, 3.41)	1.55 (0.81, 3.00)	1.85 (0.96, 3.56)
RIS 360 mg Q8W	1.96 (1.03, 3.74)^†	2.38 (1.25, 4.52)^†	2.07 (1.11, 3.88)^†	2.26 (1.21, 4.22)^†	1.59 (0.77, 3.29)	1.53 (0.74, 3.16)	1.59 (0.83, 3.06)	1.89 (0.98, 3.63)
PBO	3.53 (2.22, 5.61)^†	4.28 (2.70, 6.78)^†	4.19 (2.64, 6.65)^†	4.56 (2.87, 7.23)^†	2.93 (1.79, 4.82)^†	2.82 (1.72, 4.63)^†	3.82 (2.37, 6.15)^†	4.54 (2.82, 7.30)^†
GUS = guselkumab, HEMI = histologic endoscopic mucosal improvement, NMAs = network meta-analyses, PBO = placebo, Q4W = every four weeks, Q8W = every 8 weeks, RIS = risankizumab, UC = ulcerative colitis. *Data are presented as odds ratio (95% confidence interval). ^†Significantly favours GUS (ie, confidence interval does not include 1). Note: clinical remission is defined as a Mayo stool frequency subscore of 0 or 1 and not increased from induction baseline, Mayo rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic remission is defined as an endoscopic subscore of 0, and HEMI is defined as a combination of histologic and endoscopic improvement

Disclosure

Elise Wu, Dominik Naessens, and Mario Gomez are employees of and may hold stock/stock options in Johnson & Johnson. Ashley Bonner and Maxwell Jones are employees of EVERSANA.