EFFICACY AND SAFETY OF OBEFAZIMOD IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM TWO, PHASE 3, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 8-WEEK INDUCTION TRIALS (ABTECT-1 &AMP; 2)

Filters:

UEG Presentation

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

EFFICACY AND SAFETY OF OBEFAZIMOD IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM TWO, PHASE 3, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 8-WEEK INDUCTION TRIALS (ABTECT-1 &AMP; 2)

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

Not sure what you can access? Learn more about account types.

EFFICACY AND SAFETY OF OBEFAZIMOD IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM TWO, PHASE 3, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 8-WEEK INDUCTION TRIALS (ABTECT-1 &AMP; 2)

Bruce E. Sands 1, Silvio Danese 2, Laurent Peyrin-Biroulet 3, Marla C. Dubinsky 4, Tadakazu Hisamatsu 5, Herbert Tilg 6, Raja Atreya 7, Alessandro Armuzzi 8, Xavier Treton 9, Filip Baert 10, Ursula Seidler 11, Fabio Cataldi 12, Douglas Jacobstein 12, Christopher Rabbat 12, Kejia Shan 12, George DuVall 13, Britta Siegmund 14, Parambir Dulai 15, David T. Rubin 16, Severine Vermeire 17

Affiliations

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

2 Vita-Salute San Raffaele University - IRCCS San Raffaele Scientific Institute, Milan, Italy

3 Nancy University Hospital, Vandoeuvre-les-Nancy, France

4 Mount Sinai Kravis Children’s Hospital, New York City, United States

5 Kyorin University School of Medicine, Tokyo, Japan

6 Innsbruck Medical University - Department of Medicine, Innsbruck Medical University; Innsbruck/AT, Innsbruck, Austria

7 University Erlangen-Nuremberg, Erlangen, Germany

8 IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy

9 Groupe Hospitalier Prive Ambroise Pare – Hartmann - Institut des MICI, Neuilly sur Seine, France

10 Az Delta, Roeselare, Belgium

11 Medizinische Hochschule Klinik f. Gastroenterlogie, Hannover, Germany

12 Abivax, Paris, France

13 Tyler Research Institute, Tyler, United States

14 Charité - Universitätsmedizin Berlin, Berlin, Germany

15 Feinberg School of Medicine Northwestern University, Chicago, United States

16 University of Chicago Medicine, Chicago, United States

17 University Hospital Leuven, Leuven, Belgium

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

This summary was generated by an AI large language model based on the content transcript. It is for informational purposes only and should not be considered a substitute for clinical judgment. Always rely on your professional expertise and the full clinical context when making clinical decisions.

Abstract

Introduction

Obefazimod (Obe) is an oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and has been studied in two Phase 2 induction trials and subsequent open-label maintenance studies [1-3] in patients (pts) with moderately to severely active ulcerative colitis (UC). Here we report efficacy and safety of two Phase 3, 8-week, induction trials in adult pts with UC from ABTECT-1 [NCT05507203] and ABTECT-2 [NCT05507216].

Aims & Methods

The multicenter, randomized, double-blind, placebo-controlled ABTECT trials enrolled pts with moderate-to-severe UC (defined as modified Mayo score (MMS)≥ 5, with rectal bleeding sub-score (RBS) ≥ 1 and centrally read endoscopic score >2) who had inadequate response, loss of response, or intolerance to at least one prior therapy (with no upper limit), including corticosteroids, immunosuppressants, biologics, S1P receptor modulators and/or JAK inhibitors. Pts were randomized 2:1:1 to Obe 50 mg QD (Obe-50), Obe 25 mg QD (Obe-25) or placebo (PBO) for 8 weeks. The primary endpoint was clinical remission (per MMS) and secondary endpoints included clinical response, endoscopic improvement, symptomatic remission, and histo-endoscopic mucosal improvement (HEMI).

Results

1272 pts were randomized and treated in ABTECT-1 (636) and ABTECT-2 (636). In both trials, baseline demographics and disease characteristics were similar between groups; 45.3% and 49.3% of pts had inadequate response to 1 or more advanced therapies. A significantly higher proportion of pts receiving Obe-50 (ABTECT-1:21.7%, ABTECT-2: 19.8%) versus PBO (2.5% and 6.3%) achieved clinical remission (Obe-50-PBO difference: ABTECT-1: 19.3%, p<0.0001; ABTECT-2: 13.4%, p=0.0001) and met all key secondary endpoints in both trials. A significantly higher proportion of pts receiving Obe-25 versus PBO achieved clinical remission (Obe-25-PBO difference: 21.4%, p<0.0001) and met all key secondary endpoints in ABTECT-1. In a pooled analysis, both Obe-50 and Obe-25 met all primary and secondary endpoints with nominal significance (p<0.0001) (Table). The overall rate of serious adverse events and treatment emergent adverse events (TEAEs) leading to study drug discontinuation for pts treated with Obe were similar to PBO. Proportions of pts who reported at least one TEAE in ABTECT-1 were 59.4%, 46.9%, and 53.2% for Obe-50, Obe-25, and PBO, respectively. For ABTECT2, TEAEs occurred in 61.0%, 50.9%, and 48.4% for Obe-50, Obe-25, and PBO, respectively. The most frequent TEAE was headache (Obe-50: 20.8-25.8%; Obe-25: 14.5-15.6%; PBO: 5.7). The headaches were mild, transient, short in duration and not a barrier to treat as evidenced by a low discontinuation rate of 0-1.6%. No signal was observed for serious, severe, or opportunistic infections or malignancies.

Table: 8-week induction efficacy of obefazimod in ABTECT-1 and ABTECT-2 Phase 3 studies, and pooled ABTECT-1 and ABTECT-2^‡

	ABTECT-1					ABTECT-2					Pooled ABTECT-1 and ABTECT-2
Efficacy Endpoints at week 8, % (n)	PBO N= 158	Obe-25 N= 160	Obe-50 N= 318	Between group diff. Obe-25 vs PBO	Between group diff. Obe-50 vs PBO	PBO N= 159	Obe-25 N= 159	Obe-50 N= 318	Between group diff. Obe-25 vs PBO	Between group diff. Obe-50 vs PBO	PBO N= 317	Obe-25 N= 319	Obe-50 N= 636	Between group diff. Obe-25 vs PBO	Between group diff. Obe-50 vs PBO
Clinical remission	2.5 (4)	23.8 (38)	21.7 (69)	21.4 p<0.0001	19.3 p<0.0001	6.3 (10)	11.3 (18)	19.8 (63)	5.1 p=0.1034^¥	13.4 p=0.0001	4.4 (14)	17.6 (56)	20.8 (132)	13.2^a p<0.0001	16.4^a p<0.0001
Clinical response	28.5 (45)	65.6 (105)	61.0 (194)	37.2 p<0.0001	32.6 p<0.0001	33.3 (53)	53.5 (85)	63.2 (201)	20.1 p=0.0002^¥	29.6 p<0.0001	30.9 (98)	59.6 (190)	62.1 (395)	28.6^a p<0.0001	31.2^a p<0.0001
Endoscopic improvement†	5.7 (9)	37.5 (60)	33.3 (106)	32.0 p<0.0001	27.8 p<0.0001	10.1 (16)	22.0 (35)	35.5 (113)	12.0 p=0.0029^¥	25.4 p<0.0001	7.9 (25)	29.8 (95)	34.4 (219)	21.9^a p<0.0001	26.6^a p<0.0001
HEMI	3.2 (5)	23.8 (38)	23.0 (73)	20.7 p<0.0001	20.0 p<0.0001	7.5 (12)	13.2 (21)	23.9 (76)	5.7 p=0.0932^¥	16.4 p<0.0001	5.4 (17)	18.5 (59)	23.4 (149)	13.2^a p<0.0001	18.2^a p<0.0001
Symptomatic remission*†	17.7 (28)	42.5 (68)	41.2 (131)	24.9 p<0.0001	23.7 p<0.0001	22.0 (35)	33.3 (53)	40.3 (128)	11.4 p=0.0227	18.0 p<0.0001	19.9 (63)	37.9 (121)	40.7 (259)	18.1^a p<0.0001	21.0^a p<0.0001
NRI is used for subjects with missing outcome at Week 8 and subjects reporting any IE prior to Week 8 % Difference is for Obe minus placebo and is based on estimated common risk difference using the Mantel-Haenszel weights adjusting for the randomization stratification factors: inadequate response to advanced therapies (yes/no), baseline oral corticosteroids usage (yes/no), and region (Japan/rest of world) [ABTECT-2 only]. p-values are two sided. ^a: for pooled analysis, all p-values are nominal Clinical remission: stool frequency sub-score (SFS) ≤1, rectal bleeding sub-score (RBS) = 0 and endoscopic sub-score ≤1 Clinical response: decrease from baseline in the MMS ≥ 2 points and ≥30% from baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1 Endoscopic improvement: endoscopic sub-score ≤1 Symptomatic remission: RBS=0, SFS <1 HEMI: combination of histologic improvement (Geboes histologic score ≤3.1) and endoscopic improvement (endoscopy sub-score ≤1) * Symptomatic remission was an “other secondary” endpoint, not multiplicity controlled, for the FDA protocol † Endoscopic improvement/symptomatic remission were co-primary endpoints for the EMA protocol and were met by both doses in both trials ‡ Hierarchical testing strategy was used starting with 50mg for the primary endpoint followed by the key secondary endpoints; the 25mg was subsequently tested for the primary endpoint followed by the key secondary endpoints. ¥ 25mg did not meet the primary endpoint at week 8 in ABTECT-2 in the FDA testing protocol, therefore p-values for key secondary endpoints for the 25mg arm in ABTECT-2 are nominal

Conclusion

In both ABTECT induction trials, primary and secondary endpoints were met; obe treatment led to statistically significant improvements in clinical, endoscopic, symptomatic and combined endoscopic-histologic endpoints at week 8. Obe was well tolerated with no new safety signals identified.

References

Vermeire S, et al. J Crohns Colitis. 2023; 17: 1689-1697
Vermeire S, et al. The Lancet Gastroenterology & Hepatology. 2022; 7: 1024-1035.
Vermeire S, et al. J Crohns Colitis. 2025 ; 19 : jjaf074

Disclosure

Authors reports following potential conflicts of interest:
BES: Abbvie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Fzata, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Kaleido, Kallyope, Lilly, Merck & Co., Microba, Microbiotica, Mitsubishi Tanabe, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, OSE Immunotherapeutics, Janssen, Palisade Bio, Pfizer, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Sorriso Therapeutics, Spyre Therapeutics, Takeda, Target RWE,Teva, TLL Pharmaceutical, Tr1X, Trex Bio, Union Therapeutics, Ventyx Biosciences.
SV: AbbVie, Abivax, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG, Zealand Pharma.
LPB: Abbvie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, BMS, 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.
SD: AbbVie, Ferring, Hospira, Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer Inc, Tigenix, UCB Pharma, Vifor, Biogen, Celgene, Allergan, Celltrion, Sandoz, Boehringer Ingelheim.
PSD: Abbvie, Abivax, Adiso, Alimentiv, Bristol Meyer Squibb, Celltrion, Genentech, Geneoscopy, Janssen, Pfizer, Takeda.
MD: Abbvie, Abivax, Arena Pharmaceuticals, Astra Zeneca, Boehringer Ingelheim International GmbH, Bristol-Meyer Squibb, Eli Lilly and Company, F. Hoffmann-La Roche Ltd, Genentech Inc, Gilead, Janssen Pharmaceuticals, Merck, Pfizer Inc, Prometheus Biosciences, Takeda Pharmaceuticals.
HT: Abbvie, Abivax, Dr Falk Pharma, ferring, Galapagos, Microbiotica, MSD, Pfizer, Takeda.
BS: AbbVie, Abivax, Boehringer Ingelheim, Bristol Myers Squibb, Dr. Falk Pharma, Eli Lilly, Endpoint Health, Falk, Galapagos, Gilead, Janssen, Landos, Materia Prima, PredictImmune, Pfizer, and Takeda; AlfaSigma, CED Service GmbH, MSD, Ferring, Galapagos, Tr1x bio
TH: Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., Boston Scientific Corporation, Kissei Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., Pfizer Inc., Eli Lilly, Gilead Sciences, Bristol Myers Squibb, Abivax.
XT: Celltrion, AbbVie, Johnson & Johnson, Lilly, Takeda, Alpha Sigma, Dr. Falk, Abivax, Biogen, Fresenius Kabi, MSD, Pfizer, Tillotts, and Thabor Therapeutics.
RA: AbbVie, Abivax, AstraZeneca, Bristol-Myers Squibb, Celltrion Healthcare, Galapagos, Johnson&Johnson, Lilly, MSD, Pfizer, and Takeda Pharma
US: AbbVie, Abivax, Amgen, Galapagos, Janssen, Eli Lilly, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Gilead Sciences, Pfizer, Roche,Takeda Pharmaceuticals
AA: AbbVie, Abivax, AG Pharma, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Novartis, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma
FB: AbbVie, Amgen, Eurogenerics, J&J, Arena Pharmaceuticals, Celltrion, Ferring, Galapagos, Janssen, Merck Sharp & Dohme, Pfizer Inc, Takeda, Celgene, Fresenius Kabi, Sandoz
DTR: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx.

Event

UEG Week Berlin 2025

Topics

Gut Microbiota IBD Immunology Mechanisms & Personalised Medicine

Submission format

Late-Breaking Abstract

Session

Late-breaking trials in IBD

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

The treatment

Judith Wellens

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

Britta Siegmund

ARTIFICIAL INTELLIGENCE ENDOSCOPY SCORING DEMONSTRATES THAT TDM-BASED INFLIXIMAB DOSE-INTENSIFICATION IS SUPERIOR TO STANDARD DOSING IN PATIENTS WITH ACUTE SEVERE ULCERATIVE COLITIS: A POST-HOC ANALYSIS OF THE TITRATE STUDY

Peter Irving

COMPARISON OF ATEZOLIZUMAB PLUS BEVACIZUMAB AND DURVALUMAB PLUS TREMELIMUMAB TREATMENTS FOR ADVANCED STAGE HEPATOCELLULAR CARCINOMA IN LIVER CIRRHOSIS PATIENTS WITH CHILD-PUGH CLASS B

Fujimasa Tada

The pregnant IBD patient (Complete Session)

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

Yan Qin

UEG Presentation

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

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

Not sure what you can access? Learn more about account types.

The treatment

Judith Wellens 1

Affiliations

1 University Hospitals Leuven, Leuven, Belgium

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

Event

UEG Week Berlin 2025

Topics

IBD Primary Care

Session

When IBD and IBS experts collaborate for optimal diagnosis and treatment of IBD with IBS-like symptoms

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

The treatment

Judith Wellens

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

Britta Siegmund

ARTIFICIAL INTELLIGENCE ENDOSCOPY SCORING DEMONSTRATES THAT TDM-BASED INFLIXIMAB DOSE-INTENSIFICATION IS SUPERIOR TO STANDARD DOSING IN PATIENTS WITH ACUTE SEVERE ULCERATIVE COLITIS: A POST-HOC ANALYSIS OF THE TITRATE STUDY

Peter Irving

COMPARISON OF ATEZOLIZUMAB PLUS BEVACIZUMAB AND DURVALUMAB PLUS TREMELIMUMAB TREATMENTS FOR ADVANCED STAGE HEPATOCELLULAR CARCINOMA IN LIVER CIRRHOSIS PATIENTS WITH CHILD-PUGH CLASS B

Fujimasa Tada

The pregnant IBD patient (Complete Session)

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

Yan Qin

UEG Presentation

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

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

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

Not sure what you can access? Learn more about account types.

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

Britta Siegmund 1

Affiliations

1 Charité - Universitätsmedizin Berlin, Berlin, Germany

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

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

More Like This:

The treatment

Judith Wellens

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

Britta Siegmund

ARTIFICIAL INTELLIGENCE ENDOSCOPY SCORING DEMONSTRATES THAT TDM-BASED INFLIXIMAB DOSE-INTENSIFICATION IS SUPERIOR TO STANDARD DOSING IN PATIENTS WITH ACUTE SEVERE ULCERATIVE COLITIS: A POST-HOC ANALYSIS OF THE TITRATE STUDY

Peter Irving

COMPARISON OF ATEZOLIZUMAB PLUS BEVACIZUMAB AND DURVALUMAB PLUS TREMELIMUMAB TREATMENTS FOR ADVANCED STAGE HEPATOCELLULAR CARCINOMA IN LIVER CIRRHOSIS PATIENTS WITH CHILD-PUGH CLASS B

Fujimasa Tada

The pregnant IBD patient (Complete Session)

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

Yan Qin

UEG Presentation

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

ARTIFICIAL INTELLIGENCE ENDOSCOPY SCORING DEMONSTRATES THAT TDM-BASED INFLIXIMAB DOSE-INTENSIFICATION IS SUPERIOR TO STANDARD DOSING IN PATIENTS WITH ACUTE SEVERE ULCERATIVE COLITIS: A POST-HOC ANALYSIS OF THE TITRATE STUDY

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

Not sure what you can access? Learn more about account types.

ARTIFICIAL INTELLIGENCE ENDOSCOPY SCORING DEMONSTRATES THAT TDM-BASED INFLIXIMAB DOSE-INTENSIFICATION IS SUPERIOR TO STANDARD DOSING IN PATIENTS WITH ACUTE SEVERE ULCERATIVE COLITIS: A POST-HOC ANALYSIS OF THE TITRATE STUDY

Krisztina Barbara Gecse 1, Joep van Oostrom 1, Svend T. Rietdijk 2, Svein Oskar Frigstad 3, Glen A Doherty 4, Peter Irving 5, David Laharie 6, Floris de Voogd 1, Maarten Pruijt 1, Suzanne Anjie 1, Lotte Oldenburg 1, Adriaan Volkers 1, Lieven Mulders 1, Rossana de la Croix-Vingerling 2, Renza Koppes 2, Md Monirul Islam 3, Kristin Hammersboen Bjorlykke 7, Kine Haug 7, Carolann Coe 4, Diane Mould 8, John James 8, Chris Moore 9, Melanie Hulshoff 1, Mark Lowenberg 1, Andra Neefjes-Borst 1, Ron Mathôt 1, Esmé Clasquin 1, Kristin Kaasen Jørgensen 10, Sunny Gurm 11, Michael Byrne 11, Geert R. D'Haens 1

Affiliations

1 Amsterdam University Medical Center, Amsterdam, Netherlands

2 Onze Lieven Vrouwen Gasthuis, Amsterdam, Netherlands

3 Vestre Viken HF, Gjettum, Norway

4 University College Dublin, School of Medicine, St Vincent's Hospital, Dublin, Ireland

5 Guy´s and St Thomas´ Hospital, London, United Kingdom

6 Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France

7 Akershus Universitetssykehus, Nordbyhagen, Norway

8 Baysient LLC, Fort Meyers, United States

9 BÜHLMANN Laboratories AG, Basel, Switzerland

10 Akershus Universitetssykehus, Faculty of Medicine, University of Oslo, Nordbyhagen, Norway

11 Dova Health Intelligence, Vancouver, Canada

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

Introduction

Up to 40% of patients with acute severe ulcerative colitis (ASUC) do not respond to infliximab (IFX)(1) presumably due to insufficient drug exposure (1, 2). We investigated whether personalised IFX induction using predefined serum concentrations was superior to standard dosing.

Aims & Methods

In this prospective, multi-centre trial, adult IFX-naive steroid-refractory ASUC patients were randomised 1:1 to standard (SD) or personalised IFX dosing (PD). After an initial 5 mg/kg IFX infusion, SD was 5 mg/kg IFX at week 2 and 6. In PD, additional 5 mg/kg IFX infusions were administered guided by a Bayesian pharmacokinetic algorithm (iDose™) aiming at IFX serum concentrations >28 ug/mL day 0-28 and >15 ug/mL day 29-42 (3). The primary composite endpoint was clinical and endoscopic response at day 42 (Lichtiger score <10 and ≥3 points drop and UCEIS ≥2 points drop from baseline). Video-endoscopies were performed at baseline, day 42 and 182 and scored by 2 expert readers (XR) with adjudication by a third XR and post hoc also by the DovaVision UC AI tool (AI-R)(4). Key secondary endpoints were day 42 clinical response, day 42 endoscopic response, day 182 clinical remission (Lichtiger ≤3), day 182 endoscopic remission (UCEIS ≤1 on all components), and safety.

Results

48 patients were randomised (23 PD/25 SD) and 31 completed the 26-week study (19 PD/12 SD). Patient characteristics were comparable. Median cumulative IFX dose until day 42 was 18.41 mg/kg [1.77, 20.27] for PD vs 13.79 mg/kg [10.38, 14.82] for SD. The primary composite endpoint at day 42 was not met with XR (57% in PD vs 44% in SD; p=0.564). However, AI-R showed a significantly higher composite response rate in PD (74% in PD vs 32% in SD; p=0.0047). PD showed higher day 42 clinical response vs SD (91% vs 64%; p=0.039). Day 42 endoscopic response was observed in 57% in PD vs 44% in SD (p=0.564) with XR and 74% in PD vs 32% in SD with AI-R (p=0.0047). The proportion of patients in clinical and endoscopic remission at day 182 was higher in PD than in SD (65% vs 36%; p=0.082). Day 182 endoscopic remission with AI-R was higher in PD (52% in PD and 20% in SD; p=0.0337). SAEs occurred in 9% of patients on PD vs 20% of patients on SD. Following an interim analysis, the trial was discontinued based on futility.

Table 1. Baseline characteristics

	Personalised treatment (n=23)	Standard treatment (n=25)
Gender = Male (%)	11 (47.8)	15 (60.0)
Age (year) (median [IQR])	37.00 [24.50, 57.50]	42.00 [30.00, 56.00]
Disease duration (years) (median [IQR])	1.75 [0.62, 5.30]	6.16 [2.61, 17.21]
Naive to advanced therapy (%)	18 (78.3)	21 (84.0)
Lichtiger score (median [IQR])	14 [13, 16]	14 [12, 15]
Total Mayo score (median [IQR])	11 [11, 11]	11 [10, 11]
UCEIS (median [IQR])	6 [5, 7]	6 [5, 7]
CRP (mg/L) (median [IQR])	49.00 [35.70, 70.30]	51.00 [17.00, 105.00]
Albumin (g/L) (median [IQR])	26.00 [23.00, 30.50]	31.00 [23.00, 34.00]

Advanced therapy was defined as treatment with any biologics, JAK inhibitor or S1P modulator. IQR = interquartile range; UCEIS = Ulcerative Colitis Endoscopic Index of Severity, CRP = C-reactive protein.

Conclusion

Personalised IFX dosing was superior to standard dosing in ASUC when endoscopies were read by AI. This is the first IBD study where the primary endpoint, missed by expert assessment, was overturned and met by AI assessment instead. This demonstrates the potential of AI to fundamentally improve clinical trial methodology.

References

1. Seow CH, Newman A, Irwin SP, Steinhart AH, Silverberg MS, Greenberg GR. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010;59(1):49-54.
2. Papamichael K, Van Stappen T, Vande Casteele N, Gils A, Billiet T, Tops S, et al. Infliximab Concentration Thresholds During Induction Therapy Are Associated With Short-term Mucosal Healing in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 2016;14(4):543-9.
3. Ungar B, Mazor Y, Weisshof R, Yanai H, Ron Y, Goren I, et al. Induction infliximab levels among patients with acute severe ulcerative colitis compared with patients with moderately severe ulcerative colitis. Aliment Pharmacol Ther. 2016;43(12):1293-9.
4. Byrne M, Requa J, Panaccione R, Panes J, Bressler B, East JE, et al. Development and Validation of a novel AI-based computer vision solution for Ulcerative Colitis severity scoring on video for real world using high-volume expert-annotated video frames. United European Gastroenterol J. 2025 Oct.

Disclosure

This project received grant support from Pfizer Inc. and research support from Baysient LLC, Buhlmann Laboratories and Dova Health Intelligence.

Event

UEG Week Berlin 2025

Topics

Endoscopy IBD Mechanisms & Personalised Medicine

Submission format

Late-Breaking Abstract

Session

Hot off the press: IBD treatment

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

The treatment

Judith Wellens

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

Britta Siegmund

ARTIFICIAL INTELLIGENCE ENDOSCOPY SCORING DEMONSTRATES THAT TDM-BASED INFLIXIMAB DOSE-INTENSIFICATION IS SUPERIOR TO STANDARD DOSING IN PATIENTS WITH ACUTE SEVERE ULCERATIVE COLITIS: A POST-HOC ANALYSIS OF THE TITRATE STUDY

Peter Irving

COMPARISON OF ATEZOLIZUMAB PLUS BEVACIZUMAB AND DURVALUMAB PLUS TREMELIMUMAB TREATMENTS FOR ADVANCED STAGE HEPATOCELLULAR CARCINOMA IN LIVER CIRRHOSIS PATIENTS WITH CHILD-PUGH CLASS B

Fujimasa Tada

The pregnant IBD patient (Complete Session)

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

Yan Qin

UEG Presentation

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

COMPARISON OF ATEZOLIZUMAB PLUS BEVACIZUMAB AND DURVALUMAB PLUS TREMELIMUMAB TREATMENTS FOR ADVANCED STAGE HEPATOCELLULAR CARCINOMA IN LIVER CIRRHOSIS PATIENTS WITH CHILD-PUGH CLASS B

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

Not sure what you can access? Learn more about account types.

COMPARISON OF ATEZOLIZUMAB PLUS BEVACIZUMAB AND DURVALUMAB PLUS TREMELIMUMAB TREATMENTS FOR ADVANCED STAGE HEPATOCELLULAR CARCINOMA IN LIVER CIRRHOSIS PATIENTS WITH CHILD-PUGH CLASS B

Yuka Kimura 1, Hideko Ohama 1, Atsushi Hiraoka 1, Fujimasa Tada 1, Takeshi Hatanaka 2, Toshifumi Tada 3, Satoru Kakizaki 4, Yoichi Hiasa 5, Takashi Kumada 6

Affiliations

1 Ehime Prefectural Central Hospital, Matsuyama, Japan

2 Gunma Saiseikai Maebashi Hospital, Maebashi, Japan

3 Kobe University, Kobe, Japan

4 NHO Takasaki General Medical Center, Takasaki, Japan

5 Ehime University Graduate School of Medicine, Toon, Japan

6 Gifu Kyoritsu University, Gifu, Japan

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

Introduction

An important issue for unresectable advanced stage hepatocellular carcinoma (uHCC) patients with Child-Pugh class B liver cirrhosis (CP-B), is lack of safe treatment options that show therapeutic efficacy, thus it is considered to be an unmet need. Atezolizumab plus bevacizumab (At/Bv) and durvalumab plus tremelimumab (Dur/Tre) have each been used as first-line systemic immunotherapy for uHCC.

Aims & Methods

The present study aimed to elucidate clinical outcomes of uHCC patients with CP-B treated with those combination treatments. The records of 169 uHCC patients with CP-B in Japan, treated with At/Bv or Dur/Tre as first-line systemic therapy from 2020 to 2024 at participating institutions were examined (median age: 73 years, males: 143, Child-Pugh score 7:8:9 = 121:43:5, BCLC stage B:C = 65:104, At/Bv:Dur/Tre = 131:38). Each regimen was analyzed for therapeutic efficacy and safety, and the results compared, in a retrospective manner.

Results

Using RECIST, ver. 1.1, the objective response rate (ORR) was shown to be 25.9% in the At/Bv group, and 18.4% in the Dur/Tre group (p=0.08). Disease control rate (DCR) was significantly higher in the At/Bv group (64.9% vs. 39.5%, p=0.01). There were no significant differences between the groups for progression-free survival (PFS) [At/Bv vs. Dur/Tre=5.3 vs. 3.5 months (95% CI: 3.9–6.5 and 2.3–7.2, respectively), p=0.90], overall survival (OS) [10.5 vs. 12.5 months (95% CI: 9.1–13.3 and 7.9–NA, respectively), p=0.58], or post-progression survival (PPS) [4.9 vs. 7.5 months (95% CI: 3.7–7.5 and 2.2–NA, respectively), p=0.60]. The rate of incidence of immune-related adverse events (irAEs) of any grade was 11.5% in the At/Bv group and 23.7% in the Dur/Tre group (p=0.07), while irAEs of grade 3 or higher were noted in 3.1% and 15.8%, respectively (p=0.02) significantly greater in the Dur/Tre group).

Conclusion

The incidence rate of irAEs in each group was similar to that observed in clinical trials previously performed for these regimens. uHCC patients with CP-B, who received Dur/Tre had a greater rate of incidence of high-grade irAEs, while the At/Bv group had a better DCR, though there were no significant differences for PFS, OS, or PPS between the groups. Neither treatment was found to sufficiently improve the prognosis of uHCC patients with CP-B. Development of safe and effective treatment options for patients affected by uHCC, that can be administered even to those with CP-B remains necessary.

Disclosure

Atsushi Hiraoka: lecture fee Chugai, AstraZeneca, and Lilly.

Event

UEG Week Berlin 2025

Topics

Hepatobiliary Immunology Mechanisms & Personalised Medicine

Submission format

Abstract

Session

Bench to bedside and beyond frontiers in HCC

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

The treatment

Judith Wellens

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

Britta Siegmund

ARTIFICIAL INTELLIGENCE ENDOSCOPY SCORING DEMONSTRATES THAT TDM-BASED INFLIXIMAB DOSE-INTENSIFICATION IS SUPERIOR TO STANDARD DOSING IN PATIENTS WITH ACUTE SEVERE ULCERATIVE COLITIS: A POST-HOC ANALYSIS OF THE TITRATE STUDY

Peter Irving

COMPARISON OF ATEZOLIZUMAB PLUS BEVACIZUMAB AND DURVALUMAB PLUS TREMELIMUMAB TREATMENTS FOR ADVANCED STAGE HEPATOCELLULAR CARCINOMA IN LIVER CIRRHOSIS PATIENTS WITH CHILD-PUGH CLASS B

Fujimasa Tada

The pregnant IBD patient (Complete Session)

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

Yan Qin

UEG Presentation

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

The pregnant IBD patient (Complete Session)

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

Not sure what you can access? Learn more about account types.

The pregnant IBD patient (Complete Session)

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

Event

UEG Week Berlin 2025

Topics

IBD Paediatrics

Session

The pregnant IBD patient

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

The treatment

Judith Wellens

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

Britta Siegmund

ARTIFICIAL INTELLIGENCE ENDOSCOPY SCORING DEMONSTRATES THAT TDM-BASED INFLIXIMAB DOSE-INTENSIFICATION IS SUPERIOR TO STANDARD DOSING IN PATIENTS WITH ACUTE SEVERE ULCERATIVE COLITIS: A POST-HOC ANALYSIS OF THE TITRATE STUDY

Peter Irving

COMPARISON OF ATEZOLIZUMAB PLUS BEVACIZUMAB AND DURVALUMAB PLUS TREMELIMUMAB TREATMENTS FOR ADVANCED STAGE HEPATOCELLULAR CARCINOMA IN LIVER CIRRHOSIS PATIENTS WITH CHILD-PUGH CLASS B

Fujimasa Tada

The pregnant IBD patient (Complete Session)

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

Yan Qin

UEG Presentation

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

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

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

Not sure what you can access? Learn more about account types.

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

Affiliations

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

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

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.

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

More Like This:

The treatment

Judith Wellens

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

Britta Siegmund

ARTIFICIAL INTELLIGENCE ENDOSCOPY SCORING DEMONSTRATES THAT TDM-BASED INFLIXIMAB DOSE-INTENSIFICATION IS SUPERIOR TO STANDARD DOSING IN PATIENTS WITH ACUTE SEVERE ULCERATIVE COLITIS: A POST-HOC ANALYSIS OF THE TITRATE STUDY

Peter Irving

COMPARISON OF ATEZOLIZUMAB PLUS BEVACIZUMAB AND DURVALUMAB PLUS TREMELIMUMAB TREATMENTS FOR ADVANCED STAGE HEPATOCELLULAR CARCINOMA IN LIVER CIRRHOSIS PATIENTS WITH CHILD-PUGH CLASS B

Fujimasa Tada

The pregnant IBD patient (Complete Session)

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

Yan Qin