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Introduction

Intestinal Ultrasound (IUS) is an accurate, non-invasive technique to monitor disease activity and guide treatment decisions in inflammatory bowel disease (IBD). It has gained popularity as a point-of-care (POC) modality due to its tolerability and ease-of-use and reproducibility of results.

Aims & Methods

This study aims to assess the impact of POC IUS in daily clinical management of IBD. We conducted a single-centre retrospective cohort study of IBD patients who were evaluated with POC IUS between September 2022 and March 2023. Ultrasound data were retrieved including ultrasound reports, static images. and cine loop with doppler activity. Clinical data were retrieved from the electronic medical record. Descriptive statistics were used to evaluate characteristics of the study population. Chi-squared tests and logistic regression were used for categorical outcomes.

Results

A total of 210 IUS examinations were included in patients with Crohn’s disease (n=118, 56%), ulcerative colitis (n=90, 43%) and IBD-unclassified (n=2, 1%). The median age was 35.6years and the median disease duration was 7.0years. Fifty percent of IUS (n=105) was performed on asymptomatic patients as part of routine care; twenty-five percent (n=53) was for symptomatic patients; and twenty-three percent (n=49) was a follow-up imaging to assess response to a change in therapy. A change in management following IUS was recorded in 117 cases (55.7%).
For routine examinations (n=105), 22.9% (n=24) were abnormal, seven (7%) were referred for urgent endoscopy, thirty-five cases (33.3%) changed therapy, twenty (19%) initiated new therapy and four (4%) optimised existing therapy. Among symptomatic patients who underwent IUS (n=53), a change of medication was documented in 89% (n=47), endoscopy performed after examinations in 15% (n=8), 23% (n=12) were prescribed laxatives and 2% (n=1) were admitted to hospital.
Abnormal IUS and change in medication following IUS was higher in symptomatic than asymptomatic patients (54.7% vs 23.1%, p<0.001 and 54.7% vs 12.0%, p<0.001, respectively). Faecal calprotectin (n=105) (p=0.03) and magnetic resonance imaging (n=8) (p=0.06) results within a month prior to IUS were directly correlated with bowel wall thickness >3mm on IUS. Nineteen endoscopies were done within 1 month after examinations, which was also positively correlated with IUS result (p=0.01).

Conclusion

Our real-world study showed that POC IUS plays a role in ‘treat-to-target’ strategy in patient-management decisions, especially among symptomatic patients, allowing rapid treatment decisions. In addition to other objective markers of disease, including faecal calprotectin, POC IUS has the potential to reduce the need for more invasive endoscopic assessment of disease activity.

Disclosure

None

THE IMPACT OF POINT-OF-CARE INTESTINAL ULTRASOUND IN INFLAMMATORY BOWEL DISEASE PATIENTS

Wei Lian Tan 1, Emily Barr 1, Emi Khoo 2, Richard Fernandes 2, Hai Pham 3, Yoon-Kyo An 4, Jake Begun 2

1 Mater Hospital, Brisbane, Australia|||University of Queensland, Brisbane, Australia

2 Mater Hospital, Brisbane, Australia|||University of Queensland, Brisbane, Australia|||Mater Research Institute, Brisbane, Australia

3 University of Queensland, Brisbane, Australia|||Mater Research Institute, Brisbane, Australia

4 University of Queensland, Brisbane, Australia|||Mater Hospital, Brisbane, Australia|||Mater Research Institute, Brisbane, Australia

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Introduction

Glucagon-like peptide-2 (GLP-2) analogs stimulate adaptation of the remaining gut of patients with short bowel syndrome and intestinal failure (SBS-IF), resulting in increased intestinal absorption. Overall, preclinical data suggest intestinal permeability may be compromised in patients with SBS, which may contribute to fluid losses. However, it remains unclear whether this can be improved by GLP-2 analog treatment.

Aims & Methods

STARS Nutrition was a 52-week multicenter, open-label, phase 2 study in adult patients with SBS-IF and a colon-in-continuity (CiC) (Leuven n=7, Paris n=2) receiving weekly subcutaneous injections with the novel, long-acting GLP-2 analog apraglutide. Duodenal and sigmoid colon biopsies were collected at screening, 24 weeks, and 48 weeks of treatment. Ussing chamber experiments were performed (Leuven only) to measure the transepithelial electrical resistance (TEER) and passage of a 4 kDA fluorescently-labelled dextran molecule (FITC-D4). In addition, qRT-PCR experiments were performed for genes of tight junction- and intercellular adhesion-related proteins. Data are presented as median (min – max). Nominal p-values are calculated using Wilcoxon matched-pairs signed rank tests (significance ≤0.05).

Results

The baseline colonic TEER of 21.56 (12.50 – 28.33) Ω.cm² significantly increased to 27.22 (22.78 – 32.67) Ω.cm² (p=0.0156) at 48 weeks. In addition, the baseline FITC-D4 flux of 34.75 (19.35 – 59.03) pmol was significantly reduced to 17.42 (10.03 – 45.28) pmol (p=0.0469) at 48 weeks. There were no significant changes in gene expression in the duodenum or sigmoid colon.

Conclusion

Apraglutide in SBS-IF-CiC led to significantly improved colonic permeability, potentially contributing to its pro-adaptive effect.

Disclosure

This research was supported by VectivBio, now part of Ironwood Pharmaceuticals.

Astrid Verbiest, Joran Toth, Pauline Huyghe, Lise De Meyere, Lucas Wauters, Ricard Farré: no disclosures.
Palle Bekker Jeppesen: PBJ has received grants/research support/honoraria or consultation fees from Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast, Ferring, Fresenius Kabi, GLyPharma, Naia Pharma, NPS Pharmaceuticals, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectivBio and Zealand Pharma.
Francisca Joly: FJ has received grants/research support/honoraria or consultation fees from Baxter, Fresenius Kabi, Nestlé Health Sciences, BBraun, Theradial, Mayoli, Biocodex, mobile3e Consulting, Carembouche, NPS Pharmaceuticals, Shire, Takeda, Therachon, VectivBio and Zealand Pharma.
Tim Vanuytsel: TV has served on the speaker bureau for Fresenius Kabi, Remedus, Takeda, and VectivBio. TV has provided clinical advice to Baxter, Shire, Takeda, VectivBio, Zealand Pharma. TV has received research grants from Takeda and VectivBio.

THE GLP-2 ANALOG APRAGLUTIDE IMPROVES COLONIC BARRIER FUNCTION IN PATIENTS WITH SHORT BOWEL SYNDROME AND CHRONIC INTESTINAL FAILURE

Astrid Verbiest 1, Joran Toth 2, Pauline Huyghe 2, Lise De Meyere 1, Lucas Wauters 1, Palle Bekker Jeppesen 3, Ricard Farré 2, Francisca Joly 4, Tim Vanuytsel 1

1 University of Leuven, Leuven, Belgium|||University Hospitals Leuven, Leuven, Belgium

2 University of Leuven, Leuven, Belgium

3 Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

4 Hôpital Beaujon, University of Paris, Clichy, France

Conference

UEG Week Berlin 2025

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

Malabsorption, small intestinal pathology and failure (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Introduction

Hyperbaric oxygen therapy (HBOT) is a treatment that delivers 100% oxygen in a pressurized chamber. HBOT enhances tissue oxygenation and neovascularization and proved clinical efficacy in chronic wounds, post-radiation proctitis and enteritis, perianal fistulizing Crohn’s disease, and acute severe ulcerative colitis. Refractory ulcerative colitis (UC) remains a major therapeutic challenge.

Aims & Methods

We evaluated the tolerability, preliminary efficacy, and mechanistic effects including perfusion kinetics measured with intestinal ultrasound (IUS) of 10 and 20 sessions of HBOT in patients with UC. PARADOX was an investigator-initiated, prospective, open label, uncontrolled, dose-finding pilot trial (phase 2a) in biologic-experienced patients with moderate-to-severe, highly refractory UC with a follow-up of 26 weeks (Mayo score >5, MES ≥2, failed ≥2 classes advanced therapies). Patients (n=16; 8 per arm) continued optimized, stable dose background therapy and received 10 or 20 sessions HBOT (2.4 ATA, 120 minutes per day with two 5-minute air breaks). The primary efficacy outcome was predefined composite clinical and endoscopic response (3-point and 30% decrease in Mayo score, RB = 0 and 1-point decrease in MES) at week (W) 12. Other outcomes included tolerability; clinical, symptomatic, endoscopic, and biochemical response, and transmural response assessed by IUS including contrast-enhanced ultrasound (CEUS) to evaluate bowel wall thickness (BWT), vascularity and perfusion kinetics. Endoscopy and IUS were centrally read and adjudicated.

Results

Baseline characteristics were comparable in both cohorts with median age: 48 vs 64 years; disease duration: 12 vs 9 years; ≥4 prior advanced therapies: 3/8 in both; Mayo score: 10.5 vs 9.
At W12, the predefined composite clinical and endoscopic response rate was met in 2/8 patients with 10 sessions and 4/8 patients with 20 sessions. Clinical, endoscopic, symptomatic, biochemical, and IUS parameters all improved over time in both HBOT cohorts with a trend towards larger improvement after 20 compared to 10 sessions (See Table).
At W12, clinical responders demonstrated a significant increase in peak enhancement on CEUS compared to baseline (12.1 dB, 95% CI: 0.8 to 34.3), while non-responders showed a numerical decrease (–5.4 dB, 95% CI: –20.9 to 4.0). This divergent trajectory was consistent across perfusion parameters related to both wash-in and wash-out (e.g., time to peak, wash-in and wash-out rate, area under the curve), suggesting a treatment-related vascular response. In contrast, early gains in non-responders had waned by W12. This effect was numerically larger after 20 sessions, supporting a potential dose–response effect.
HBOT was well tolerated with no dose-limiting toxicities.

Week-12 efficacy results	10 sessions HBOT N = 8	20 sessions HBOT N = 8	(adjusted) Risk Ratio (95% CI)	P-value
Composite clinical and endoscopic response (W12), n (%)	2 (25)	4 (50)	1.7 (0.4 - 4.2)	.31
Clinical remission (W12), n (%)	0	3 (38)	5.2 (0.6 - 49)	.2
Clinical response (W12), n (%)	3 (38)	6 (75)	1.7 (0.4 - 4.2)	.31
Endoscopic improvement (W12), n (%)	0	3 (38)	5.2 (0.6 - 50)	.2
Symptomatic remission (W12), n (%)	4 (50)	4 (50)	0.8 (0.2 - 4.2)	.68
Symptomatic response (W12), n (%)	4 (50)	6 (75)	1.3 (0.4 - 3.9)	.45
Fecal calprotectin at BL, µg/g, mean (95% CI) change from BL-W12, EMM (95 % CI)	1020 (312 - 3370) –631 (–2086 to –194)	735 (223 - 2444) –542 (–1809 to –164)	-	.76
Bowel Wall Thickness of sigmoid (mm) at BL, mean (95% CI) change from BL-W12, EMM (95% CI)	4.2 (2.8 - 5.6) –0.44 (–1.15 to 0.28)	3.9 (2.8 - 5.1) –0.25 (–0.93 to 0.43)	-	.69
Color Doppler Signal of sigmoid, mLimberg ≥2, n (%) at least 1-point improvement from BL-W12, n (%)	2 (25) 3 (38)	4 (50) 3 (38)	1.1 (0.6 – 2.0)	.66

Conclusion

HBOT is a feasible adjunctive therapy in treatment-refractory moderate-severe UC. CEUS showed improved intestinal perfusion in HBOT responders, which offers promising non-invasive tools for response assessment. These findings provide a rationale for a randomized dose-optimized phase 2 trial with potentially longer duration of treatment.

HYPERBARIC OXYGEN THERAPY IN REFRACTORY ULCERATIVE COLITIS: A PROSPECTIVE PILOT TRIAL

Lieven Mulders 1, Maarten Pruijt 1, Joep van Oostrom 1, Esmerij van der Zanden 2, Andra Neefjes-Borst 1, Pim J Koelink 1, Manon E. Wildenberg 1, Wouter J. de Jonge 1, Milan Ridderikhof 3, Rob van Hulst 3, Geert R. D'Haens 1, Krisztina B. Gecse 1

1 Amsterdam UMC, Amsterdam, Netherlands

2 Amstelland Ziekenhuis, Amstelveen, Netherlands

3 Amsterdam UMC, Amsterdam, Netherlands|||Amsterdam UMC, Amsterdam, Netherlands

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

Treatment outcomes in IBD (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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EFFICACY AND SAFETY OF MORF-057 THERAPY IN ADULTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: PHASE 2B EMERALD-2 STUDY RESULTS THROUGH WEEK 12

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Introduction

MORF-057 is an oral α₄β₇ integrin inhibitor that prevents immune cell entry into the gut to alleviate inflammation.

Aims & Methods

EMERALD-2 is a phase 2b, randomized, double-blind, placebo-controlled study evaluating MORF-057 efficacy and safety in adults with moderately to severely active ulcerative colitis (UC). Participants with Modified Mayo Score (MMS) 5–9, inadequate/loss of response or intolerance to conventional or advanced therapy (AT), and who were integrin inhibitor-naïve received 1 of 3 MORF-057 doses or placebo (1:1:1:1). The primary efficacy endpoint was clinical remission at Week 12; secondary and exploratory efficacy endpoints were rates of clinical response and endoscopic improvement, respectively. Pharmacokinetic and pharmacodynamic endpoints and safety were evaluated. The study is registered with ClinicalTrials.gov (NCT05611671).

Results

The study enrolled 280 participants (mean [SD] age, 40.2 [14.6] years; 55.4% male; mean [SD] time since UC diagnosis, 6.7 [7.2] years). At baseline, mean (SD) MMS was 6.7 (1.0); 39.3% of participants were on a stable corticosteroid dose, 20.4% were on an immunomodulator, and 31.1% were AT-experienced.
Clinical remission rate with MORF-057 at Week 12 was dose dependent, ranging from 17.1% (100 mg QD) to 31.9% (200 mg BID) vs. 24.3% with placebo (Table 1), with the same trend in the AT-experienced subgroup (N=87; 100 mg QD, 4.3%; 100 mg BID, 13.6%; 200 mg BID, 21.1%; placebo, 13.0%). Compared with placebo, 200 mg BID MORF-057 had numerically higher clinical response and endoscopic and histo-endoscopic mucosal improvement (HEMI) rates, with the latter 2 endpoints showing an increasing trend with higher doses.

Table 1. Efficacy endpoints in EMERALD-2 at Week 12

Rate (proportion of patients, %)	MORF-057			Placebo (n=70)
Rate (proportion of patients, %)	100 mg QD (n=70)	100 mg BID (n=71)	200 mg BID (n=69)	Placebo (n=70)
Clinical Remission^a	17.1	23.9	31.9	24.3
Clinical Response^b	57.1	53.5	62.3	54.3
Endoscopic Improvement^c	31.4	32.4	43.5	31.4
Histo-Endoscopic Mucosal Improvement^d	27.1	31.0	42.0	25.7

^aBased on MMS (stool frequency=0/1, RB=0, MES=0/1 [excluding friability]). Non-significant vs. placebo.
^b≥2-point reduction in MMS and ≥30% change from baseline, and ≥1-point reduction in RB score from baseline or RB=0/1.
^cMES≤1.
^dMES=0/1 (excluding friability) and neutrophil infiltration in <5% of crypts; no crypt destruction; and no erosions, ulcerations, or granulation tissue (Geboes scoring).
MES, Mayo Endoscopic Subscore; MMS, Modified Mayo Score; RB, rectal bleeding.

There was a dose-dependent increasing trend in α4β7 receptor occupancy. Treatment-emergent adverse events (TEAEs) in the MORF-057 groups were mostly of mild (42/76, 55.3%) or moderate (25/76, 32.9%) severity; TEAE frequency was similar to the placebo group (36.0% [pooled rate for 3 dose regimens] vs. 34.8%). Among all participants, there were 5 serious AEs not considered treatment-related (UC exacerbation [n=2], AST increase, pneumothorax, vertebral disc herniation). There were no cases of progressive multifocal leukoencephalopathy or meaningfully increased absolute lymphocyte count and no deaths.

Conclusion

Dose-dependent responses to MORF-057 were observed for clinical remission and hard-to-achieve endpoints such as HEMI at Week 12. The clinical remission rate with MORF-057 was numerically higher but did not achieve statistical significance vs. placebo, which showed higher-than-expected responses. MORF-057 had a favorable safety profile with no meaningful safety findings. The study is ongoing to evaluate maintenance safety and efficacy, with further clinical development of MORF-057 planned.

Disclosure

BES: Honoraria for consulting--AbbVie, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Fresenius Kabi, Fzata, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck & Co., Microbiotica, Mitsubishi Tanabe, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, OSE Immunotherapeutics, Palisade Bio, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Sorriso Therapeutics, Spyre Therapeutics, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences. Consulting and speaking fees--Abivax. Consulting and speaking fees and other support--Eli Lilly and Company. Research grants, consulting and speaking fees, and other support--Bristol Myers Squibb, Eli Lilly and Company, Janssen, Pfizer, Takeda. Research grants and consulting fees--Janssen. Stock/stock options--Ventyx Biopharma.
BGF: Senior Scientific Director at Alimentiv Inc. Consulting--AbbVie, Abivax, Adiso, AgomAB Therapeutics, Akros, Alira Health, Ally Bridge Group, AnaptysBio, Apini Therapeutics, Argenx, Attovia Tx, Avoro Capital Advisors, Belmore Law, BioFactura, BioJamp, Biora Therapeutics, Blackbird Laboratories, Boehringer-Ingelheim, Boxer Capital, Celsius Therapeutics, Celgene/Bristol Myers Squibb, Celltrion, Clarivate, Connect BioPharma, Disc Medicine, Duality, EcoR1, Eli Lilly and Company, Ensho Therapeutics, Equillium, Evida, Enveda, Faes Farma, First Wave, Forbion, Galapagos, Galen Atlantica, Genentech/Roche, General Atlantic, Genesis Therapeutics, Gilead, Gossamer Pharma, GSK, Imhotex, ImmiDomics, Immunic Therapeutics, Intercept, Janssen, Japan Tobacco Inc., Klick Health, LifeMine Therapeutics, Mage Biologics, Merck, Mestag, Mirador Therapeutics, Mobius Care, Monte Rosa Tx, Morphic Therapeutics, Nexys Therapeutics, Nighthawk Therapeutics, Nimbus Therapeutics, Novartis, OncoC4, OrbiMed, Orphagen, Palisade Bio, Pendopharm, Pfizer, Protagonist,32 Bio, REDX, Roche, Roivant/Televant, Sanofi, Sobi, Sorriso, Spyre Therapeutics, SRT Therapeutics, Sun Pharma, Surrozen Inc., Synedgen, Takeda, Teva, Triastek, Trex Bio, TR1X Inc. TVM Lifesciences, Ventyx Biosciences, Versant Ventures, Vida Ventures, Zagbio. Speaker's Bureau--AbbVie, Janssen, Takeda. Scientific Advisory Board (DSMB)--AbbVie, AnaptysBio, Boehringer-Ingelheim, Celgene/Bristol Myers Squibb, Eli Lilly and Company, Genentech/Roche, Janssen, Merck, MiroBio, Origo BioPharma, Pfizer, REDX Pharma, Sanofi, Takeda, Teva, Ecor1Capital, Morphic, GSK. Stock shareholder--Connect BioPharma, EnGene. Provided expert testimony--Belmore Law.
SS: Received fees--AbbVie, Amgen, Arena, Biogen, Bristol Meyers Squibb, Celgene, Celltrion, Falk, Ferring, Fresenius Kabi, Galapagos, Gilead, IMAB, Janssen, Eli Lilly and Company, MSD, Mylan, Novartis, Pfizer, Protagonist, Provention Bio, Roche, Sandoz/Hexal, Shire, Takeda, Ventyx.
LP-B: Consulting--AbbVie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, Bristol Myers Squibb, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, Ysopia. Grants--Celltrion, Fresenius Kabi, Medac, MSD, Takeda. Lectures--AbbVie, Alfasigma, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Janssen, Kern Pharma, Eli Lilly and Company, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots, Viatris. Travel support--AbbVie, Alfasigma, Amgen, Celltrion, Connect Biopharm, Ferring, Galapagos, Genentech, Gilead, Gossamer Bio, Janssen, Eli Lilly and Company, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer, Tillots.
SD: Consultancy fees--AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly and Company, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor. Lecture fees--AbbVie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda.
BA, MC, YW, SKL, MM, AW, XZ, NME: Employees and stockholders of Eli Lilly and Company.

EFFICACY AND SAFETY OF MORF-057 THERAPY IN ADULTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: PHASE 2B EMERALD-2 STUDY RESULTS THROUGH WEEK 12

Bruce E. Sands 1, Brian G. Feagan 2, Stefan Schreiber 3, Brihad Abhyankar 4, Michael Choi 5, Yujun Wu 5, Sun Ku Lee 5, Maloy Mangada 5, Andrew Wey 5, Xin Zhang 5, Nadezhda Mincheva Eberhart 5, Laurent Peyrin-Biroulet 6, Silvio Danese 7

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

2 Alimentiv Inc., London, Canada

3 University Hospital Schleswig-Holstein, Kiel, Germany

4 Eli Lilly and Company Limited, Basingstoke, United Kingdom

5 Eli Lilly and Company, Indianapolis, United States

6 Centre Hospitalier Régional Universitaire de Nancy, Nancy, France

7 Vita-Salute San Raffaele University - IRCCS Ospedale San Raffaele, Milan, Italy

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine

Submission format

Abstract

Session

Advanced therapies in ulcerative colitis

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Introduction

Mesalazine suppositories are recommended in guidelines for the induction and maintenance of remission in patients with ulcerative proctitis (UP). Nevertheless, nonadherence can be frequent and the recommended dose of mesalazine suppositories in maintenance treatment remains unknown.

Aims & Methods

The aim of this study was to determine the frequency of non-adherence to mesalazine suppositories, evaluate potential factors for nonadherence and the impact on quality of life and number of relapses in patients with UP.
Methods: A multicenter, prospective observational study was designed in patients ≥18 years old with UP under maintenance treatment with mesalazine suppositories (Claversal© 500 mg, Pentasa© 1g or Salofalk©1g). We evaluated adherence, socio-demographic data and complications associated with poor adherence at 6 and 12 months. Adherence was assessed by tracking pharmacy refills (medication possession ratio, MPR). We defined good adherence as MPR ≥80% over 12 months. Health-Related Quality of Life (HRQoL) was evaluated using the disease-specific shortened Spanish version of the IBDQ (SIBDQ-9). Relapse was defined as partial Mayo ≥2; biological remission as a partial Mayo score <2 and fecal calprotectin ≤150. Multivariate analysis allowed us to determine the risk factors for non-adherence to mesalazine suppositories.

Results

A total of 188 patients with mean age 51 were consecutively included across 14 Spanish hospitals (Table 1). Of these, mean MPR was 76% and 56% presented MPR ≥80%. Mean age was higher among patients with MPR ≥80% (p=0.045). A total of 125 (71,4%) patients were in biological remission, 31 patients (16%) had a relapse and 3 (1.6%) patients were hospitalized during the follow-up. The use of corticosteroids during the follow-up (OR=4.25, p=0.041) were associated with better adherence. There were no differences between the different brands and doses of suppositories analyzed. Low adherence was not related with increased number of flares (p=0.927), hospitalizations (p=0.225) or decreased quality of life (p = 0.353) over the 12 months of follow-up.

Conclusion

Almost half of patients with UP on maintenance treatment with mesalazine suppositories have low adherence. The use of oral corticosteroids during the follow-up may increase adherence, but poor adherence to mesalazine suppositories was not related with risk of relapse, hospitalizations or worst quality of life.

Disclosure

Manuel Barreiro de Acosta: speaker, consultant and advisory member for or have received research funding from AbbVie, Janssen, Takeda, Pfizer, Lilly, Alphasigma, Sandoz and Oncostellae

ADHERENCE TO MESALAZINE SUPPOSITORIES MAINTENANCE TREATMENT IN PATIENTS WITH ULCERATIVE PROCTITIS: MESUPO MULTICENTER PROSPECTIVE OBSERVATIONAL STUDY FROM GETECCU

Rocío Ferreiro-Iglesias 1, Laura Nieto-Garcia 2, Maria Luisa De Castro Parga 3, Pablo Perez Galindo 4, Alejandro Hernández-Camba 5, María José García 6, María Calvo Íñiguez 7, Iago Rodríguez-Lago 8, Eva Martí-Marqués 9, Ainara Iriarte 10, Hector Pallares Manrique 11, Carmen Dueñas Sadornil 12, Lucía Zabalza San Martín 13, Patricia Ramírez de la Piscina Urraca 14, Lorena Rodríguez-Alonso 15, Iria Bastón-Rey 16, Jesús Martínez-Cadilla 17, Daniel Carpo 18, Ana Álvarez Cancelo 19, María del Sol Porto-Silva 2, Yamile Zabana 20, Manuel Barreiro de Acosta 1

1 Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain|||University Hospital of Santiago de Compostela, Santiago de Compostela, Spain

2 Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain

3 Complexo Hospitalario Universitario de Vigo CHUVI, Vigo, Spain|||Galicia Sur Health Research Institute ISS Galicia Sur, Vigo, Spain

4 Galicia Sur Health Research Institute ISS Galicia Sur, Vigo, Spain|||Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain

5 Complejo Hospitalario Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain

6 Hospital Universitario Marqués de Valdecilla and IDIVAL, Santander, Spain|||University of Cantabria, Santander, Spain

7 Hospital Universitario San Pedro, Logroño, Spain

8 Hospital Universitario de Galdakao, Bilbao, Spain|||Instituto de Investigación Sanitaria Biobizkaia- Galdakao, Bilbao, Spain

9 University Hospital Lucus Augusti, Lugo, Spain

10 Hospital Zumárraga- OSI Goierri-Alto Urola, Guipúzkoa, Spain

11 Hospital Juan Ramón Jiménez, Huelva, Spain

12 University Hospital of Caceres, Cáceres, Spain

13 Hospital Universitario de Navarra, Pamplona, Spain|||Instituto de Investigación de Navarra idiSNA, Navarra, Spain

14 Hospital Universitario de Álava, Álava, Spain

15 Hospital Universitari De Bellvitge, L’Hospitalet del Llobregat, Spain

16 University Hospital of Santiago de Compostela, Santiago de Compostela, Spain|||Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain

17 Galicia Sur Health Research Institute ISS Galicia Sur, Vigo, Spain|||Complexo Hospitalario Universitario de Vigo CHUVI, Vigo., Spain

18 Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain|||Galicia Sur Health Research Institute ISS Galicia Sur, Vigo, Spain

19 Hospital Universitario Marqués de Valdecilla and IDIVAL, Santander, Spain

20 Hospital Universitari Mútua Terrassa and CIBERhed, Terrassa, Spain|||Universitat Autónoma de Barcelona, Barcelona, Spain

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

IBD (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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COMBINED TNF AND OX40L BLOCKADE DEMONSTRATES EFFICACY IN A MURINE ADOPTIVE T CELL TRANSFER MODEL OF COLITIS

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Introduction

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are characterized by dysregulated T-cell responses, causing chronic intestinal inflammation.¹ While anti-TNF therapy is established in IBD, targeting additional pathways may improve outcomes for patients who do not respond adequately to current treatments.² OX40L, an immune co-stimulator, has been implicated in the pathogenesis of several inflammatory conditions.³ Our study provides a comprehensive analysis of the effects of combined TNF and OX40L blockade in a murine adoptive T cell transfer (ATC) model of colitis, examining body weight, detailed histopathological parameters, and a broad range of inflammatory cytokines in colon tissue.

Aims & Methods

Colitis was induced in severe combined immunodeficiency (SCID) mice by intraperitoneal transfer of CD4⁺CD45RB^high T cells isolated from healthy BALB/c donor mice. We established five treatment groups (n=8-10): 1) CD45RB^low transfer “healthy control”, 2) CD45RB^high transfer with isotype antibodies “disease control group”, 3) CD45RB^high transfer with anti-TNF antibody (XT3.11, 250 μg/mouse), 4) CD45RB^high transfer with anti-OX40L antibody (RM134L, 250 μg/mouse), and 5) CD45RB^high transfer with both antibodies at 250 µg/mouse, each. Body weight was monitored for 46 days as a measure of disease progression and normalized to baseline weight at day 1. At study termination, we collected colon tissue for analysis of inflammatory cytokines using multiplex immunoassays and conducted histopathological examination. Histopathological scoring was performed blinded using a validated scoring system for colonic inflammation.⁴

Results

Overall, combined anti-TNF/anti-OX40L therapy was most effective in preventing body weight loss compared to the isotype disease control group, followed by anti-TNF monotherapy and anti-OX40L monotherapy (p<0.0001, p=0.0009, and p=0.03, respectively). Mean normalized body weight (MNBW) of the CD45RB^low healthy control group at termination on day 46 was 115.2 %, while CD45RB^high cell transfer in the disease control group triggered disease induction and body weight loss, with a MNBW of 93.8 % at day 46. The CD45RB^high groups treated with anti-TNF or anti OX40L monotherapy reached a MNBW of 107.6 % and 102.9%, respectively. The CD45RB^high group treated with combination therapy reached 112.6%, closest to the CD45RB^low healthy control group. Notably, only combination therapy led to a significant improvement in histopathological scoring (p=0.0176) compared to the isotype disease control. Similarly, combination treatment consistently resulted in the strongest downregulation of several inflammatory cytokines including IFNg, IL-4, or TNFa, which are increased in colon tissue in the CD45RB^high disease group compared to the CD45RB^low healthy control group.

Conclusion

Combined blockade of TNF and OX40L demonstrated significantly greater efficacy in the ATC preclinical model of IBD in prevention of weight loss, downregulation of key inflammatory cytokines, and reduction of histological damage compared to either monotherapy. These data suggest potential additive efficacy for TNF and OX40L inhibition in controlling intestinal inflammation, and warrant further exploration of dual TNF/OX40L inhibition in clinical trials, particularly among those with inadequate response to anti-TNF monotherapy.

References

1. Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol. 2010;28:573-621.
2. Vermeire S. Combination biologic therapy for ulcerative colitis. Lancet Gastroenterol Hepatol. 2023;8:288-90.
3. Fu Y, Lin Q, Zhang Z, Zhang L. Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity. Acta Pharm Sin B. 2020;10:414-33.
4. Erben U, Loddenkemper C, Doerfel K, Spieckermann S, Haller D, Heimesaat MM, Zeitz M, Siegmund B, Kühl AA. A guide to histomorphological evaluation of intestinal inflammation in mouse models. Int J Clin Exp Pathol. 2014;7:4557-76.

Disclosure

Thomas Leeuw, Rolf Keiffer, Danping Ding-Pfennigdorff, Christian Asbrand, Raaj Mehta, Matthias Herrmann are employees of Sanofi and may hold stock or equity options in Sanofi

COMBINED TNF AND OX40L BLOCKADE DEMONSTRATES EFFICACY IN A MURINE ADOPTIVE T CELL TRANSFER MODEL OF COLITIS

Thomas Leeuw 1, Rolf Keiffer 1, Danping Ding-Pfennigdorff 1, Christian Asbrand 1, Raaj Mehta 2, Matthias Herrmann 1

1 Immunology & Inflammation Research TA, Sanofi Germany, Frankfurt, Germany

2 Immunology & Inflammation TA, Sanofi US, Cambridge, United States

Event

UEG Week Berlin 2025

Topics

IBD Immunology Mechanisms & Personalised Medicine

Submission format

Abstract

Session

Unexpected novel therapies tackling intestinal inflammation

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Poster

Standard Poster

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Introduction

Few studies have evaluated the efficacy of butyric acid in treating children with inflammatory bowel disease (IBD).

Aims & Methods

In children and adolescents with recently diagnosed IBD, the purpose of this research was to assess the efficacy of oral sodium butyrate as an adjunct to conventional treatment.This trial was unicentric, prospective, randomised, and placebo controlled. 150 mg sodium butyrate single dose (group A) or a placebo (group B) were randomly assigned to patients with ulcerative colitis or Crohn's disease aged 7–18 years who were receiving conventional medication based on the severity of their conditions. Disease activity, C-reactive protein (CRP), and faecal calprotectin concentration differences between the two study groups at 12 weeks of the trial were the main outcomes.

Results

With 44 patients in group A and 44 in group B, 88 individuals with initially active illness finished the research. Most patients experienced remission by week 12 of the study (36 patients in Group A with sodium butyrate-82%, and 11 patients in Group B with placebo-48%). Between the two groups, a significant difference in disease activity was seen (p = 0.001), with a signifigant higher percent of cases in remission among those from lot A that received sodium butirate compared to placebo. The sodium butyrate group appeared to have less systemic inflammation than the other group, as evidenced by the significantly lower CRP levels in Group A (18.14 ± 11.19 mg/L) compared to Group B (57.00 ± 33.28 mg/L) at 12 weeks (T2) (P < 0.001). No negative effects were recorded by any of the patients. Fecal calprotectin in Group A dropped much more after 12 weeks (T2) (P < 0.001), suggesting that the sodium butyrate group was better able to regulate intestinal inflammation.

Conclusion

In newly diagnosed children and adolescents with IBD, a 12-week sodium butyrate supplementation did demonstrate effectiveness as an additional treatment and decreased the rate of relapsing cases.