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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)

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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

Two Phase 3 induction trials (ABTECT-1 and ABTECT-2) demonstrated that obefazimod 50 mg once daily achieved statistically significant clinical remission at week 8 in patients with moderate-to-severe ulcerative colitis, including those with multiple prior therapy failures.

In ABTECT-1, obefazimod 50 mg achieved 21.7% clinical remission versus 2.5% placebo (difference 19.3%, p<0.0001); in ABTECT-2, 19.8% versus 6.3% placebo (difference 13.4%, p=0.0001).
Obefazimod 50 mg met all key secondary endpoints in both trials, including clinical response (61.0-63.2%), endoscopic improvement (33.3-35.5%), and histo-endoscopic mucosal improvement (23.0-23.9%).
The 25 mg dose met the primary endpoint and all secondary endpoints in ABTECT-1 but did not meet the primary endpoint in ABTECT-2 (11.3% vs 6.3% placebo, p=0.1034).
The most common adverse event was headache (20.8-25.8% with 50 mg, 14.5-15.6% with 25 mg, 5.7% placebo), which was mild, transient, and led to discontinuation in only 0-1.6% of patients.
No signal was observed for serious, severe, or opportunistic infections or malignancies; overall serious adverse events and discontinuation rates were similar to placebo.
Study population included 45.3-49.3% with inadequate response to one or more advanced therapies, with no upper limit on prior treatment failures.

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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

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Peter Irving

UEG Presentation

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The treatment

Judith Wellens 1

Affiliations

1 University Hospitals Leuven, Leuven, Belgium

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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

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Judith Wellens

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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

UEG Presentation

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

Innovations in IBD Therapy: The Story of TL1A - from Discovery to Potential Future Care (F. Hoffmann-La Roche Ltd) (Complete Session)

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Innovations in IBD Therapy: The Story of TL1A - from Discovery to Potential Future Care (F. Hoffmann-La Roche Ltd) (Complete Session)

Jean-Frédéric Colombel 1, Beatriz Gros 2, Remo Panaccione 3

Affiliations

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

2 Hospital Universitario Reina Sofia, Cordoba, Spain

3 University of Calgary, Calgary, Canada

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Abstract

Publisher

F. Hoffmann La Roche

Event

UEG Week Berlin 2025

Session

Innovations in IBD Therapy: The Story of TL1A - from Discovery to Potential Future Care (F. Hoffmann-La Roche Ltd)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Remo Panaccione

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Federica Di Vincenzo

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Knut E.A. Lundin

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Chris Lamb

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

UEG Presentation

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

"I am a little better, doctor": When is 'better' enough in ASUC

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

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"I am a little better, doctor": When is 'better' enough in ASUC

Federica Di Vincenzo 1

Affiliations

1 Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy

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Abstract

Event

UEG Postgraduate Teaching Programme Berlin 2025

Topics

IBD Surgery

Session

When the alarm bells go off: Approach to acute severe colitis

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Judith Wellens

Innovations in IBD Therapy: The Story of TL1A - from Discovery to Potential Future Care (F. Hoffmann-La Roche Ltd) (Complete Session)

Remo Panaccione

"I am a little better, doctor": When is 'better' enough in ASUC

Federica Di Vincenzo

ANTI-TNF TREATMENT WITHDRAWAL IN ULCERATIVE COLITIS, A MULTICENTER, OPEN-LABEL, RANDOMIZED CONTROLLED TRIAL

Knut E.A. Lundin

... for medical therapy in inflammatory bowel diseases

Chris Lamb

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

UEG Presentation

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

ANTI-TNF TREATMENT WITHDRAWAL IN ULCERATIVE COLITIS, A MULTICENTER, OPEN-LABEL, RANDOMIZED CONTROLLED TRIAL

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

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ANTI-TNF TREATMENT WITHDRAWAL IN ULCERATIVE COLITIS, A MULTICENTER, OPEN-LABEL, RANDOMIZED CONTROLLED TRIAL

Ingrid Prytz Berset 1, Frode Lerang 2, Dag Arne Lihaug Hoff 3, Knut E.A. Lundin 4

Affiliations

1 Gastroenterology Aalesund, Alesund, Norway

2 Central Hosspital of Ostfold, Grålum, Norway

3 Aalesund Hospital, Møre & Romsdal Hospital trust, Aalesund, Norway

4 K. G. Jebsen Coeliac Disease Research Centre, University of Oslo and Oslo University Hospital, Oslo, Norway

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Abstract

Introduction

The BIOSTOP Trial is a prospective, multicenter, randomized, controlled, open-label study conducted in Norway to evaluate the two-year outcomes of tumor necrosis factor-alpha (anti-TNF) antibody withdrawal in patients with ulcerative colitis (UC) in sustained clinical and endoscopic remission. Prior non-randomized studies have suggested that approximately half of such patients maintain remission after anti-TNF discontinuation and that reintroduction of anti-TNF therapy is generally effective and safe in the event of relapse.

Aims & Methods

A total of 174 UC patients in confirmed clinical and endoscopic remission were enrolled across 19 gastroenterology centers between June 2017 and December 2020 and randomized 1:1 to either continue or discontinue anti-TNF therapy. Eligibility criteria included at least 12 months of first-line anti-TNF maintenance treatment, clinical remission, fecal calprotectin <200 µg/g, and endoscopic remission (Mayo endoscopic score 0 or 1). Two-year follow-up data were available for 172 patients (86 in each group). In 156 of the patients endoscopies were available for central reading (77 in the withdrawal group and 79 in the maintenance group). The primary endpoint was sustained endoscopic remission at two years.

Results

At two years, central reading of follow-up colonoscopies confirmed endoscopic remission in 64 of 77 patients (83%, 95% CI 71.8 – 93.1) in the anti-TNF withdrawal group, compared to 77 of 79 patients (96 %, 95 % CI 92.1 – 100.8) in the anti-TNF maintenance group. The non-inferiority primary endpoint of the study was thus not met. During the study period, 48% of patients in the withdrawal group and 88% in the maintenance group remained in sustained clinical and endoscopic remission without relapse. Among the 45 patients in the withdrawal group who experienced endoscopic confirmed relapse, 28 (62%) resumed anti-TNF therapy, with 26 achieving both clinical and endoscopic remission. Additionally, 10 of 13 patients with mild relapses achieved endoscopic remission with optimized non-biologic therapy. There were no difference in serious adverse events between the groups.

Conclusion

After two years, 83% of patients in the anti-TNF withdrawal group and 96% in the maintenance group were in clinical and endoscopic remission, including those who experienced flares and achieved new remission after reintroduction of anti-TNF or optimized non-biologic therapy. Nearly half of the patients maintained remission without anti-TNF, and the majority of relapses were effectively managed. These findings suggest that anti-TNF withdrawal is a safe option for selected UC patients in confirmed remission, provided they are monitored closely.
Trial Registration: ClinicalTrials.gov Identifier: NCT03011268; EudraCT Number: 2016-001409-18. Trial completion date: 31 January 2025.

Disclosure

No disclosures

Event

UEG Week Berlin 2025

Topics

Endoscopy IBD

Submission format

Abstract

Session

Tackling IBD in clinics

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

The treatment

Judith Wellens

Innovations in IBD Therapy: The Story of TL1A - from Discovery to Potential Future Care (F. Hoffmann-La Roche Ltd) (Complete Session)

Remo Panaccione

"I am a little better, doctor": When is 'better' enough in ASUC

Federica Di Vincenzo

ANTI-TNF TREATMENT WITHDRAWAL IN ULCERATIVE COLITIS, A MULTICENTER, OPEN-LABEL, RANDOMIZED CONTROLLED TRIAL

Knut E.A. Lundin

... for medical therapy in inflammatory bowel diseases

Chris Lamb

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

UEG Presentation

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

... for medical therapy in inflammatory bowel diseases

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... for medical therapy in inflammatory bowel diseases

Chris Lamb 1

Affiliations

1 Newcastle Hospitals NHS Foundation Trust, Newcastle, United Kingdom

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Abstract

Event

UEG Week Berlin 2025

Topics

Colorectal IBD Surgery

Session

Predicting patient outcomes...

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Chris Lamb

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

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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

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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

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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

Innovations in IBD Therapy: The Story of TL1A - from Discovery to Potential Future Care (F. Hoffmann-La Roche Ltd) (Complete Session)

Remo Panaccione

"I am a little better, doctor": When is 'better' enough in ASUC

Federica Di Vincenzo

ANTI-TNF TREATMENT WITHDRAWAL IN ULCERATIVE COLITIS, A MULTICENTER, OPEN-LABEL, RANDOMIZED CONTROLLED TRIAL

Knut E.A. Lundin

... for medical therapy in inflammatory bowel diseases

Chris Lamb

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