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DYNAMICS OF HEPATITIS B CORE-RELATED ANTIGEN DURING POST-TREATMENT MONITORING TO PREDICT CLINICAL RELAPSE FOLLOWING CESSATION OF NUCLEOS(T)IDE ANALOGS

Jaw-Town Lin 1, Ying Nan Tsai 2, Jia-Ling Wu 3, Cheng-Hao Tseng 4, Chieh-Chang Chen 5, Yu-Jen Fang 6, Tzeng-Huey Yang 7, Yao-Chun Hsu 2

Affiliations

1 E-Da Hospital, Kaohsiung, Taiwan, Province of China

2 E-Da Hospital/I-Shou University, Kaohsiung, Taiwan, Province of China

3 National Cheng Kung University, Tainan, Taiwan, Province of China

4 E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan, Province of China

5 NTUH, Taipei, Taiwan, Province of China

6 National Taiwan University Yun-Lin Branch, Yun-Lin, Taiwan, Province of China

7 Lotung Poh-Ai Hospital, Yilan, Taiwan, Province of China

Summary

AI Generated

In a multicenter study of 203 chronic hepatitis B patients who stopped nucleos(t)ide analog therapy, dynamic HBcrAg measurement predicted clinical relapse risk with levels below 1,000 U/mL associated with lower relapse rates.

Clinical relapse (ALT > 80 U/L with recurrent viremia) occurred in 104 of 203 patients during median follow-up of 31.7 months, with 5-year cumulative incidence of 54.8%
Time-varying HBcrAg levels significantly predicted subsequent clinical relapse (adjusted hazard ratio 1.43 per log U/mL, 95% CI 1.16-1.76) after adjusting for end-of-treatment HBsAg, anti-HBe antibody, and ALT
HBcrAg levels below 1,000 U/mL during follow-up were associated with substantially lower risk of clinical relapse (adjusted hazard ratio 0.31, 95% CI 0.17-0.57)
All patients had negative HBeAg and undetectable HBV DNA at treatment cessation after median 36.9 months of entecavir or tenofovir therapy
This multicenter analysis suggests HBcrAg monitoring may help guide post-treatment surveillance strategies in patients discontinuing nucleos(t)ide analog therapy

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Abstract

Introduction

Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative strategy for chronic hepatitis B (CHB), but data on optimal biomarkers for post-treatment monitoring is limited.

Aims & Methods

With the aim to investigate whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR), this retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase (ALT) > 80 U/L with recurrent viremia. During follow-up, serum HBcrAg was evaluated as a time-varying variable in the Cox proportional hazard model.

Results

The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.1% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5-40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7-67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1% ‐ 62.4%). Time-varying HBcrAg levels were a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.43 per log U/mL; 95% CI, 1.16-1.76) in the multivariable model adjusted for EOT HBsAg level, anti-HBe antibody, and EOT ALT. During follow-up, HBcrAg < 1,000 U/mL predicted a low risk of subsequent CR (aHR, 0.31; 95% CI, 0.17-0.57).

Conclusion

Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be used to guide posttreatment monitoring.

References

1. Mak LY, Wong DK, Cheung KS, Seto WK, Lai CL, Yuen MF. Review article: Hepatitis B core-related antigen (HBcrAg): an emerging marker for chronic hepatitis B virus infection. Aliment Pharmacol Ther. 2018;47(1):43-54.
2. Hsu YC, Nguyen MH, Mo LR, Wu MS, Yang TH, Chen CC, et al. Combining hepatitis B core-related and surface antigens at end of nucleos(t)ide analogue treatment to predict off-therapy relapse risk. Aliment Pharmacol Ther. 2019;49(1):107-15.
3. Sonneveld MJ, Park JY, Kaewdech A, Seto WK, Tanaka Y, Carey I, et al. CREATE Study Group. Prediction of Sustained Response After Nucleo(s)tide Analogue Cessation Using HBsAg and HBcrAg Levels: A Multicenter Study (CREATE). Clin Gastroenterol Hepatol. 2022 Apr;20(4):e784-e793

Conference

UEG Week Copenhagen 2023

Topics

Hepatobiliary

Submission format

Abstract

Session

Prognosis and prediction in liver disease (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

More Like This:

BBT003, A NOVEL IL-23P19 X TL1A BISPECIFIC ANTIBODY WITH EXTENDED HALF-LIFE, DEMONSTRATES A POTENTIAL BEST-IN-DISEASE PROFILE IN PRECLINICAL MODELS OF INFLAMMATORY BOWEL DISEASE

Shanshan Xu

UEG Online Courses x UEG Podcast: Oesophageal Cancer

Ana-Maria Bucalau

Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Omer Ahmad

A PHASE 2A STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND CLINICAL EFFICACY OF ORAL TREATMENT WITH MBF-118 IN PATIENTS WITH FIBROSTENOSING CROHN’S DISEASE

Cristina Balagué

STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Philippe Wiesel

REAL-WORLD PERFORMANCE OF BSG FRAILTY SCORE SYSTEM TO ASSESS LONG-TERM OUTCOMES AFTER ENDOSCOPIC RESECTION OF LARGE COLORECTAL POLYPS

Maria Pellisé Urquiza

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BBT003, A NOVEL IL-23P19 X TL1A BISPECIFIC ANTIBODY WITH EXTENDED HALF-LIFE, DEMONSTRATES A POTENTIAL BEST-IN-DISEASE PROFILE IN PRECLINICAL MODELS OF INFLAMMATORY BOWEL DISEASE

Wei Liang 1, Jingjing Jiang 1, Tianhang Zhai 2, Jia Song 2, Weifeng Huang 2, Xiaoniu Miao 2, Andy Tsun 2, Thang Ho 1, Shanshan Xu 1

Affiliations

1 Bambusa Therapeutics, Boston, United States

2 Biotheus Inc., Zhuhai, China

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Abstract

Introduction

Interleukin-23 (IL-23) is a key driver of chronic intestinal inflammation primarily through sustaining the pathogenic Th17 immune response. Tumor necrosis factor–like cytokine 1A (TL1A), via engaging death receptor 3 (DR3), further amplifies pro-inflammatory Th1/Th17 responses and promotes fibroblast activation, contributing to intestinal fibrosis. Clinical data indicate that inhibition of either IL-23 or TL1A alone can induce remission in inflammatory bowel disease (IBD). Simultaneous targeting of both pathways offers the potential to more comprehensively suppress inflammation and fibrosis, enabling deeper and more durable disease control. BBT003 is an innovative “1+1” human IgG1 bispecific antibody designed to co-inhibit IL-23 and TL1A, incorporating Fc engineering for half-life extension. This study evaluated BBT003 in preclinical in vitro and in vivo models relevant to IBD pathogenesis.

Aims & Methods

Target binding affinity of BBT003 was measured by biolayer interferometry and ELISA. Ability of BBT003 to block IL-23- and/or TL1A-induced signaling pathways and biological functions was assessed in cell-based assays. In vivo efficacy was evaluated in a TNBS-induced colitis model using hTL1A/hIL23A/hIL12B knock-in mice. Safety was evaluated in cynomolgus monkeys.

Results

BBT003 bound human IL-23 and TL1A with high affinities in the subnanomolar range. BBT003 potently inhibited IL-23 interaction with IL-23R. It robustly and selectively inhibited TL1A interaction with DR3 while sparing binding to the decoy receptor DcR3, potentially preserving endogenous regulatory control of TL1A activity. This TL1A receptor-selective profile was not observed with tulisokibart or afimkibart analogues and was more pronounced than that of a duvakitug analogue. In cell-based assays, BBT003 completely inhibited IL-23-induced STAT3 signaling and IL-17A expression, as well as TL1A-induced NF-κB signaling, TF-1 cell apoptosis, and IFN-γ expression in human peripheral blood mononuclear cells. Simultaneous dual-target binding and blockade were demonstrated, resulting in enhanced suppression of IL-17A release from mouse splenic lymphocytes co-stimulated with human IL-23 and TL1A, compared with single-targeting monoclonal antibodies (mAbs). In the TNBS-induced mouse colitis model, BBT003 outperformed single-targeting mAbs including guselkumab and tulisokibart analogues, and demonstrated dose-dependent, statistically significant efficacy in reducing disease activity index, colon histopathology, inflammation and fibrosis while restoring body weights. Additionally, BBT003 bound monkey IL-23 and TL1A with affinities comparable to those observed for human target proteins. In cynomolgus monkeys, BBT003 was well tolerated at the highest tested dose under repeat-dose conditions, providing a wide safety margin to support clinical development.

Conclusion

Dual blockade of the IL-23 and TL1A pathways by BBT003 demonstrates the potential to achieve better efficacy over single-targeting mAbs in IBD, with enhanced inhibition of in vitro biological functions and superior in vivo anti-inflammatory/anti-fibrotic and disease-modifying effects in preclinical models. Tolerability at the highest tested dose in cynomolgus monkeys suggests potentially a wide therapeutic window in humans. Its half-life extension technology further supports the potential for more convenient dosing and improved durability of clinical benefits in patients with IBD.

Event

UEG Week Barcelona 2026

Topics

Mechanisms & Personalised Medicine IBD

Submission format

Abstract

Session

Looking into the future: Novel therapeutics in IBD (Part 2)

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

BBT003, A NOVEL IL-23P19 X TL1A BISPECIFIC ANTIBODY WITH EXTENDED HALF-LIFE, DEMONSTRATES A POTENTIAL BEST-IN-DISEASE PROFILE IN PRECLINICAL MODELS OF INFLAMMATORY BOWEL DISEASE

Shanshan Xu

UEG Online Courses x UEG Podcast: Oesophageal Cancer

Ana-Maria Bucalau

Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Omer Ahmad

A PHASE 2A STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND CLINICAL EFFICACY OF ORAL TREATMENT WITH MBF-118 IN PATIENTS WITH FIBROSTENOSING CROHN’S DISEASE

Cristina Balagué

STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Philippe Wiesel

REAL-WORLD PERFORMANCE OF BSG FRAILTY SCORE SYSTEM TO ASSESS LONG-TERM OUTCOMES AFTER ENDOSCOPIC RESECTION OF LARGE COLORECTAL POLYPS

Maria Pellisé Urquiza

UEG Podcast Episode

UEG Podcast

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UEG Online Courses x UEG Podcast: Oesophageal Cancer

Roos E. Pouw, Ana-Maria Bucalau

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Abstract

Topics

Digestive Oncology Oesophagus

Published

2026

More Like This:

BBT003, A NOVEL IL-23P19 X TL1A BISPECIFIC ANTIBODY WITH EXTENDED HALF-LIFE, DEMONSTRATES A POTENTIAL BEST-IN-DISEASE PROFILE IN PRECLINICAL MODELS OF INFLAMMATORY BOWEL DISEASE

Shanshan Xu

UEG Online Courses x UEG Podcast: Oesophageal Cancer

Ana-Maria Bucalau

Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Omer Ahmad

A PHASE 2A STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND CLINICAL EFFICACY OF ORAL TREATMENT WITH MBF-118 IN PATIENTS WITH FIBROSTENOSING CROHN’S DISEASE

Cristina Balagué

STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Philippe Wiesel

REAL-WORLD PERFORMANCE OF BSG FRAILTY SCORE SYSTEM TO ASSESS LONG-TERM OUTCOMES AFTER ENDOSCOPIC RESECTION OF LARGE COLORECTAL POLYPS

Maria Pellisé Urquiza

UEG Presentation

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Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

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Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Marcello Fabio Maida 1, Omer Ahmad 2

Affiliations

1 Department of Medicine and Surgery, University of Enna ‘Kore’, Enna, Italy

2 University College London, London, United Kingdom

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Abstract

Event

Postgraduate Teaching Programme Barcelona 2026

Session

AI integration in my clinical practice today

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

BBT003, A NOVEL IL-23P19 X TL1A BISPECIFIC ANTIBODY WITH EXTENDED HALF-LIFE, DEMONSTRATES A POTENTIAL BEST-IN-DISEASE PROFILE IN PRECLINICAL MODELS OF INFLAMMATORY BOWEL DISEASE

Shanshan Xu

UEG Online Courses x UEG Podcast: Oesophageal Cancer

Ana-Maria Bucalau

Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Omer Ahmad

A PHASE 2A STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND CLINICAL EFFICACY OF ORAL TREATMENT WITH MBF-118 IN PATIENTS WITH FIBROSTENOSING CROHN’S DISEASE

Cristina Balagué

STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Philippe Wiesel

REAL-WORLD PERFORMANCE OF BSG FRAILTY SCORE SYSTEM TO ASSESS LONG-TERM OUTCOMES AFTER ENDOSCOPIC RESECTION OF LARGE COLORECTAL POLYPS

Maria Pellisé Urquiza

UEG Presentation

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A PHASE 2A STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND CLINICAL EFFICACY OF ORAL TREATMENT WITH MBF-118 IN PATIENTS WITH FIBROSTENOSING CROHN’S DISEASE

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A PHASE 2A STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND CLINICAL EFFICACY OF ORAL TREATMENT WITH MBF-118 IN PATIENTS WITH FIBROSTENOSING CROHN’S DISEASE

Manuel Barreiro de Acosta 1,2, Iria Bastón-Rey 1,2, María del Sol Porto-Silva 1,2, Laura Nieto-Garcia 1,2, Rocío Ferreiro-Iglesias 1,2, Cristina Calviño Suarez 2,1, Rodolfo Rodríguez 3, Richard Roberts 3, Luc Marti 3, Cristina Balagué 3

Affiliations

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

2 University Hospital of Santiago de Compostela, Santiago de Compostela, Spain

3 Medibiofarma S.L, Pamplona, Spain

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Abstract

Introduction

PPARγ full agonists show anti-fibrotic and anti-inflammatory effects; however, their adverse event profile limits long-term use. To maintain efficacy and improve safety, MBF-118 is being developed as an oral PPARγ partial agonist for fibrostenosing Crohn’s disease (CD). In preclinical models and healthy volunteers, MBF-118 showed good safety and tolerability with a differentiated toxicity profile. We report results of a phase 2a study assessing safety, tolerability, pharmacokinetics and preliminary efficacy.

Aims & Methods

In this open-label proof-of-concept trial (EU CT 2022-501464-18-00), adults with fibrostenosing CD received MBF-118 (100 or 200 mg daily) for 28 days. Eligibility required ≥1 imaging-confirmed stenosis and stable CD therapy, including biologics (anti-TNFα, anti-integrin, anti-IL-12/23). Stenosis was assessed by ultrasound and endoscopy at baseline and end of treatment. Patients on low dose entered a 90-day extension. Preliminary efficacy by assessed clinical parameters including Crohn’s disease activity index (CDAI) scores and clinical response through endoscopy and ultrasound imaging. All potential adverse events (AEs) were recorded. Secondary objectives included confirming the compound’s systemic and tissue pharmacokinetic profile, and pharmacodynamic response through changes to systemic adiponectin levels.

Results

Five patients received 100 mg MBF-118 daily and five patients received 200 mg, daily. No placebo was used. Patients’ age ranged from 29-73 years (n = 10, Mean 48.3±14.1), and 60% were diagnosed with CD before the age of 40. Six patients (60%) had undergone at least one surgical resection for CD prior to enrolment. All ten patients (100%) were on stable biological therapy prior to enrolment and presented clinical remission at baseline (CDAI mean score 32±23, range 4-72).
During either the 84-day (28 treatment days, 54 follow-up days) or 132-day (90 treatment days, 42 follow-up days) observation period, no serious AEs nor treatment-related AEs leading to discontinuation were reported. Almost all AEs were tabulated as mild (grade 1). No AEs were deemed related to the use of MBF-118. There were no clinically relevant changes in vital signs, laboratory values or ECG parameters which raise any safety concerns.
Pharmacokinetic analysis indicated steady-state plasma concentrations were reached and therapeutically relevant levels in colonic and ileal biopsy tissue, confirming GI tissue distribution of MBF-118. Increases in plasma adiponectin levels confirmed a pharmacodynamic effect of MBF-118 at both dose levels.
An improvement in the scores of the Abdominal Pain and Stool Frequency Instrument (PRO-2, 50% of patients) and the Numeric Rating Scale for abdominal pain (NRS-11, 40% of patients) was observed. Other clinical readouts remained stable throughout the treatment periods of 1 or 3 months. By imaging, 3 patients showed a reduction in pre-stenotic dilation, 3 patients showed an increase in lumen diameter and 2 patients showed a reduction in stenotic length.

Conclusion

Oral MBF-118 was well tolerated during ether the 4-week or 13-week treatment period. Its excellent safety profile, GI tissue distribution and promising trends of clinical activity may provide a potential therapeutic option for the treatment and/or management of fibrosis in Crohn’s disease patients.

Disclosure

The corresponding author is also a medical consultant for Medibiofarma. The remaining authors have no potential conflicts of interest to disclose

Event

UEG Week Barcelona 2026

Topics

Mechanisms & Personalised Medicine IBD

Submission format

Abstract

Session

Looking into the future: Novel therapeutics in IBD (Part 2)

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

BBT003, A NOVEL IL-23P19 X TL1A BISPECIFIC ANTIBODY WITH EXTENDED HALF-LIFE, DEMONSTRATES A POTENTIAL BEST-IN-DISEASE PROFILE IN PRECLINICAL MODELS OF INFLAMMATORY BOWEL DISEASE

Shanshan Xu

UEG Online Courses x UEG Podcast: Oesophageal Cancer

Ana-Maria Bucalau

Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Omer Ahmad

A PHASE 2A STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND CLINICAL EFFICACY OF ORAL TREATMENT WITH MBF-118 IN PATIENTS WITH FIBROSTENOSING CROHN’S DISEASE

Cristina Balagué

STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Philippe Wiesel

REAL-WORLD PERFORMANCE OF BSG FRAILTY SCORE SYSTEM TO ASSESS LONG-TERM OUTCOMES AFTER ENDOSCOPIC RESECTION OF LARGE COLORECTAL POLYPS

Maria Pellisé Urquiza

UEG Presentation

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STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

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STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Florian Rieder 1, Cathy Lu 2, Anja Poulsen 3, Walter Reinisch 4, Jaroslaw Kierkus 5, Elena Ricart 6, Joel Flechter 7, Jordi Rimola 8, Pieter-Jan Stiers 9, Kim Thys 9, Margreke Brill 9, Silke Hüttner 9, Rolf Van Heeswijk 9, Andrea Saez 10, Tim Van Kaem 9, Philippe Wiesel 11

Affiliations

1 Cleveland Clinic Foundation, Cleveland Heights, United States

2 University Of Calgary, Calgary, Canada

3 Rigshospitalet, Copenhagen Ø, Denmark

4 Medical University of Vienna, Wien, Austria

5 Children’s Memorial Health Institute, Warsaw, Poland

6 Hospital Clinic, Barcelona, Spain

7 Mayo Clinic, Rochester, United States

8 Hospital Clínic Barcelona, Barcelona, Spain

9 Agomab Therapeutics NV, Berchem, Belgium

10 Agomab Spain S.L.U., A Coruña, Spain

11 Agomab US, Cambridge, United States

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Abstract

Introduction

Ontunisertib is an oral GI-restricted ALK5 inhibitor blocking the TGFβ pathway, and is in development for treatment of fibrostenosing Crohn's disease (FSCD). A challenge in developing FSCD therapies is the lack of validated objective endpoints. STENOVA is a randomized trial conducted in FSCD. We present imaging results of the 12-week placebo-controlled Part A and an update on the ongoing open-label treatment extension (OLE; Part B; preliminary data).

Aims & Methods

Adults with symptomatic FSCD with at least 1 MRE-confirmed ileal stricture were randomized to receive ontunisertib 200mg BID, 100mg QD, or placebo (PBO) for 12 weeks in Part A. Participants completing Part A could receive ontunisertib 200mg BID for up to 48 weeks in Part B (launched during Part A). In Part A, ileocolonoscopy and MRE were performed at baseline and Week 12. In Part B OLE, ileocolonoscopy is planned at Week 48 and MRE at Weeks 24 and 48. Both are centrally evaluated, using SES-CD and stricture-related items, respectively.

Results

Part A included 103 participants (34/34/35 in the 200mg/100mg/PBO groups), 92 completed treatment. In total, 49 participants were included in Part B OLE (16/19/14 from the 200mg/100mg/PBO groups of Part A, 94% of eligible participants). At the analysis cut-off date, 44 participants were ongoing and 24 completed the first 24 weeks of OLE treatment.
Part A achieved its primary endpoint, with ontunisertib for 12 weeks being generally well tolerated. Data from Part B until the cut-off date supports the longer-term safety and tolerability profile of ontunisertib.
In Part A, an improvement in SES-CD was observed at Week 12 in the 200mg BID group. In this group, SES-CD showed higher endoscopic response and remission rate, and a higher proportion of participants with non-passable strictures at baseline had passable strictures at Week 12. The SES-CD, particularly the narrowing component, demonstrated robust inter-reader agreement. In the 200mg BID and 100mg QD groups, MRE items showed trends towards stricture improvement compared to PBO. This was most evident for stricture length, the item with the highest reliability and strongest correlation with overall disease severity.
Over the first 24-week period in Part B OLE, a continued trend for improvement in MRE stricture length was observed in participants originally randomized to ontunisertib. In participants who transitioned from PBO, the worsening stricture length observed in Part A ceased to progress and stabilized during Part B OLE.

Conclusion

Treatment with ontunisertib for up to 36 weeks was generally well tolerated. Positive trends in endoscopic and MRE outcomes were observed. The data suggest that ontunisertib has potential to be suitable for chronic dosing and may provide a therapeutic option for FSCD patients. These outcomes contribute to the FSCD field by advancing the validation of objective endpoints.

Disclosure

Tim Van Kaem, submitting author is an employee of Agomab Therapeutics.

Event

UEG Week Barcelona 2026

Topics

Mechanisms & Personalised Medicine IBD

Submission format

Abstract

Session

Looking into the future: Novel therapeutics in IBD (Part 2)

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

BBT003, A NOVEL IL-23P19 X TL1A BISPECIFIC ANTIBODY WITH EXTENDED HALF-LIFE, DEMONSTRATES A POTENTIAL BEST-IN-DISEASE PROFILE IN PRECLINICAL MODELS OF INFLAMMATORY BOWEL DISEASE

Shanshan Xu

UEG Online Courses x UEG Podcast: Oesophageal Cancer

Ana-Maria Bucalau

Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Omer Ahmad

A PHASE 2A STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND CLINICAL EFFICACY OF ORAL TREATMENT WITH MBF-118 IN PATIENTS WITH FIBROSTENOSING CROHN’S DISEASE

Cristina Balagué

STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Philippe Wiesel

REAL-WORLD PERFORMANCE OF BSG FRAILTY SCORE SYSTEM TO ASSESS LONG-TERM OUTCOMES AFTER ENDOSCOPIC RESECTION OF LARGE COLORECTAL POLYPS

Maria Pellisé Urquiza

UEG Presentation

New

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

REAL-WORLD PERFORMANCE OF BSG FRAILTY SCORE SYSTEM TO ASSESS LONG-TERM OUTCOMES AFTER ENDOSCOPIC RESECTION OF LARGE COLORECTAL POLYPS

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

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REAL-WORLD PERFORMANCE OF BSG FRAILTY SCORE SYSTEM TO ASSESS LONG-TERM OUTCOMES AFTER ENDOSCOPIC RESECTION OF LARGE COLORECTAL POLYPS

Oswaldo Ortiz 1, Angelo Brunori 1,2, Joaquín Castillo Iturra 1,2, Laura Arandes Bellosta 2, Maria Daca Alvarez 1,2, Liseth Rivero Sánchez 1, Maria Pellisé Urquiza 1,2

Affiliations

1 Hospital Clínic de Barcelona, Barcelona, Spain

2 Universitat de Barcelona, Barcelona, Spain

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Abstract

Introduction

Polypectomy has widely demonstrated to reduce incidence and mortality of colorectal cancer. However, large resections are not exempt from complications and risks especially in fragile/comorbid patients. The British Society of Gastroenterology (BSG) published in 2025 a guidance based on predictive models have been developed determine the optimal management of lesions in patients with limited life expectancy based on Charlson comorbidity index (CCI) [1]. Our aim is to describe long-term follow up outcomes in terms of mortality and complications after endoscopic management of colorectal polyps ≥20 mm and compare it with the risk categories proposed by the BSG 2025 guidance.

Aims & Methods

Retrospective single-center cohort study including patients planned for endoscopic resection of colorectal polyps >20 mm between 2013-2017. Of 396 eligible patients, 395 with follow-up were analyzed. Baseline patient and polyp characteristics, post-procedural complications, and all-cause mortality were described. Mortality was assessed with Cox regression models. A descriptive comparison with the BSG frailty score was performed according to CCI. Multivariable logistic regression was used to identify factors associated with post-procedural complications.

Results

The median follow-up for the whole cohort was 9.17 years (IQR 7.53-10.69). During follow-up, 96/395 patients (24.3%) died. Estimating a theorical 2.5-5.6% annual transition rate from advanced adenoma to CRC patients with CCI ≥5 did not receive a clear benefit from the endoscopic resection in terms of survival in our cohort. Among individual CCI comorbidities, chronic pulmonary disease (HR 1.68, 95% CI 1.00-2.82) and liver disease (HR 4.08, 95% CI 1.58-10.59) were associated with mortality. Post-procedural complications occurred in 42/395 (10.6%); 37/42 (88.1%) required hospitalization and 4/42 (9.5%) surgery. In the multivariable analysis antiplatelet therapy was independently associated with complications (OR 2.65, 95% CI 1.13-6.20.

Conclusion

In our cohort, CCI index may overestimate mortality in subgroup scored CCI≥5. Despite this, this subgroup still does not appear to benefit from endoscopic resection in terms of survival when compared with the theoretical risk of progression to CRC. Antithrombotic therapy was strongly associated with adverse outcomes and confirmed its importance in decision making. Prospective comparative studies including both treated and conservatively managed patients are needed to define the true benefit-risk balance of endoscopic treatment for large colorectal polyps in individuals in grey zone (CCI 5).

References

[1] Rutter MD, Ranjan R, Westwood C, et al BSG/ACPGBI guidance on the management of colorectal polyps in patients with limited life expectancy Gut 2025;74:1551-1560.

Event

UEG Week Barcelona 2026

Topics

Digestive Oncology Endoscopy Colorectal

Submission format

Abstract

Session

Endoscopic resection: Cut, cure, prevent

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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