PREGNANCY AND INFANT OUTCOMES FOLLOWING IN UTERO EXPOSURE TO JAK INHIBITORS IN WOMEN WITH INFLAMMATORY BOWEL DISEASE: A GLOBAL MULTICENTER COHORT STUDY

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PREGNANCY AND INFANT OUTCOMES FOLLOWING IN UTERO EXPOSURE TO JAK INHIBITORS IN WOMEN WITH INFLAMMATORY BOWEL DISEASE: A GLOBAL MULTICENTER COHORT STUDY

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PREGNANCY AND INFANT OUTCOMES FOLLOWING IN UTERO EXPOSURE TO JAK INHIBITORS IN WOMEN WITH INFLAMMATORY BOWEL DISEASE: A GLOBAL MULTICENTER COHORT STUDY

Mette Julsgaard 1, Simon Mark Dahl Baunwall 2, Cynthia Seow 3, Dana Duricova 4, Sunanda Kane 5, Neha Zacharias 6, Rupert W Leong 7, Bel Klaartje Kok 8, Anna Kagramanova 9, Barbora Pipek 10, Kristina Candido 11, Rachel Cooney 12, Rafal Filip 13, Vytautas Kiudelis 14, Michal Konecny 15, Daniela Pugliese 16, Genoile Silva 17, Edoardo Vincenzo Savarino 18, Brigita Smolovic 19, Sophie Vieujean 20, Shu-Chen Wei 21, Uma Mahadevan 22

Affiliations

1 Aarhus University Hospital, Aarhus N, Denmark|||Aarhus University, Aarhus N, Denmark

2 Aarhus University Hospital, Aarhus N, Denmark

3 University of Calgary, Calgary, Canada

4 ISCARE I.V.F. a.s., Prague, Czechia

5 Mayo Clinic, Rochester, Rochester, United States

6 Hull University Teaching Hospitals, Hull, United Kingdom

7 Concord Repatriation General Hospital, Sydney, Australia|||Macquarie University, Sydney, Australia

8 Barts Health NHS Trust, London, United Kingdom

9 A. S. Loginov Moscow Clinical Scientific Center, Moscow, Balaschiha, Russian Federation|||Research Institute of Health Organization and Medical Management, Moscow, Russian Federation

10 Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, Czechia|||Hospital AGEL Vitkovice, Ostrava, Czechia

11 McGill University, Montreal, Canada

12 University Hospital Birmingham NHS Trust, Birmingham, United Kingdom

13 Regional Hospital No. 2 in Rzeszow, Rzeszów, Poland|||University of Rzeszow, Rzeszow, Poland

14 Lithuanian University of Health Sciences, Kaunas, Lithuania

15 Palacky University and University Hospital Olomouc, Olomouc, Czechia

16 Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy|||Università Cattolica del Sacro Cuore, Rome, Italy

17 Universidade do Estado da Bahia, Salvador, Bahia, Brazil

18 University of Padua, Division of Gastroenterology, Padua, Italy

19 Faculty of Medicine, University of Montenegro, Podgorica, Montenegro

20 University Hospital CHU of Liège, Liège, Belgium

21 National Taiwan University Hospital, Taipei City, Taiwan, Province of China

22 University of California, San Francisco, United States

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Abstract

Introduction

JAK inhibitors (JAKi) are small molecules capable of crossing the placenta via passive diffusion or active extracellular transport from early pregnancy.¹ Data on the risks of in utero JAKi exposure are limited,² particularly regarding pregnancy outcomes, infant infections, vaccine responses, and childhood development.

Aims & Methods

We conducted a multicenter retrospective JAKi and pregnancy observational study supported by the ECCO Collaborative Network for Exceptionally Rare Case Reports (CONFER). Pregnant women with inflammatory bowel disease (IBD) exposed to tofacitinib (TOFA), upadacitinib (UPA), or filgotinib (FILGO) during pregnancy were enrolled from 21 centers across 15 countries. Data collected included maternal demographics, IBD characteristics, disease activity, medication use - including timing and duration of JAKi exposure - along with maternal, pregnancy, and infant outcomes.

Results

Of 43 JAKi exposed pregnancies, 17 (39.5%) were unplanned. Disease activity was present in 22 (51.2%) of the pregnancies. One-in-five women initiated JAKi in pregnancy (n=8, 18.6%). Abortion occurred in 8 cases, at a median gestational age (GA) of 8.5 weeks (range 3-16). Of these, 3 (7.0%) were spontaneous and 5 (11.6%) induced, with two terminations due to concerns about potential adverse effects of JAKi treatment. Of the remaining 35 pregnancies 26 (74.3%) were exposed to TOFA (5 mg BID (n=9), 10 mg BID (n=17)), 8 (22.9%) to UPA (30 mg daily (n=2), 45 mg daily (n=6)) and one (2.9%) to FILGO (200 mg daily). The majority received JAKi treatment throughout pregnancy (n=24, 68.6%). Discontinuation of JAKi during the 1^st or 2^nd trimester was followed by disease activity in 7 of 11 cases (63.6%). Maternal complication risk was low: no cases of DVT or (pre)eclampsia; premature rupture of membranes (GA 34–37) occurred in 3 cases, and 4 women required hospitalization due to infection or other complications. Among 35 live births, one infant (2.9%) was preterm (GA 34), three (8.6%) were small for gestational age, one (2.9%) had an Apgar score <7 at 5 minutes, and no congenital abnormalities were reported. Follow-up infant data are shown in table 1. One-third of breastfeeding women continued JAKi treatment. A high adherence rate to the national immunization schedule was seen. Three (8.6%) skipped the live rotavirus vaccine due to in uteroJAKi exposure. No adverse effects were reported following live attenuated or inactivated vaccines, and no malignancies were observed.

Table 1. Follow-up in 31 infants after in utero exposure to JAK-inhibitors
	n	(%)	Notes
Duration, months – median (range)	17	(1-88)
Proportion of breastfeeding women (n=24) who continued JAKi treatment	7	(29.2)
Infection resulting in hospitalization (age 0-4 months)	2	(6.5)	Moderate-to-severe maternal disease activity treated with systemic corticosteroids and initiation of upadacitinib at gestational weeks 8 and 28, respectively. No infection-related sequelae.
Normal development	31	(100)
Follow the national immunization program	26	(74.3)
Live BCG vaccine provided (age 0-1 month)	5	(16.1)	No adverse effects reported.
Live Rotavirus vaccine provided (age 1.5-6 months)	13	(41.9)	No adverse effects reported.
Live MMR vaccine provided (age ≥ 12 months)	13	(41.9)	No adverse effects reported.

Conclusion

In this global multicenter study of JAKi exposure during pregnancy in women with IBD, maternal complication rates were low, and no increased risk of adverse pregnancy outcome were observed among live births. While disease activity was common, particularly following early discontinuation of JAKi, infant outcomes - including development, infection risk, and vaccine response - were reassuring. These findings provide important preliminary safety data to guide decision-making regarding the use of JAKi in pregnancy, though further prospective studies are needed to confirm long-term safety.

References

1. Fein KC, Arral ML, Kim JS, et al. Placental drug transport and fetal exposure during pregnancy is determined by drug molecular size, chemistry, and conformation. J Control Release 2023;361:29-39.
2. Torres J, Chaparro M, Julsgaard M, et al. European Crohn's and Colitis Guidelines on Sexuality, Fertility, Pregnancy, and Lactation. J Crohns Colitis 2023;17:1-27.

Disclosure

M. Julsgaard: Advisory board for AbbVie. G. Santana: Speaker and advisory board for pfizer.

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine

Submission format

Abstract

Session

Clinical management of IBD

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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UEG Standards and Guidelines

Clinical Practice Guideline

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European Society for the Study of Coeliac Disease (ESsCD) 2025 Updated Guidelines on the Diagnosis and Management of Coeliac Disease in Adults. Part 2: Management, Follow-Up, and Complex Disease Courses

Abdulbaqi Al-Toma

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Guideline

ABSTRACT

Introduction

Since the publication of the first European Society for the Study of Coeliac Disease (ESsCD) guidelines in 2019, substantial advances have been made in understanding the management and complex disease courses of coeliac disease (CeD) in adults. These 2025 updated guidelines aim to integrate new evidence, refine management strategies, and promote a personalised and multidisciplinary approach to care.

Methods

The ESsCD convened a multidisciplinary panel of experts to revise the 2019 guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) framework. Evidence was appraised and graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Statements and recommendations were draughted within working groups and finalised through a structured Delphi consensus process.

Results

The updated guidelines are presented in two parts. Part 1, which has already been published, addresses the diagnostic approach to CeD in adults, whereas Part 2 focuses on disease management, structured follow-up, and the evaluation and treatment of persistent symptoms despite a gluten-free diet or refractory disease. New or expanded sections include guidance on the safe inclusion of oats, use of low-FODMAP diets in patients with persistent symptoms, management of exocrine pancreatic insufficiency, recognition of functional asplenia and related vaccination recommendations, and stratified bone-health screening. The guidelines also discuss nutritional and psychosocial support, digital models of care, and structured transition from paediatric to adult services. Updated therapeutic strategies for refractory CeD are provided, including immunosuppressive and novel pharmacologic options.

Conclusions

These updated guidelines offer a comprehensive, evidence-based framework for the management and follow-up of adults with CeD. By integrating recent scientific advances with pragmatic, patient-centred recommendations, they seek to optimise clinical outcomes, quality of life, and long-term health in individuals with CeD.

Guideline

Clinical Practice Guideline

Topics

Immunology Small Intestine & Nutrition

Citation

United European Gastroenterology Journal, 2026

Published

2026

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Peter Irving

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Eva Visser

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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

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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

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Eva Visser

The pregnant IBD patient (Complete Session)

UEG Presentation

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

Fistulising Crohn's disease: Underlying mechanism

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Fistulising Crohn's disease: Underlying mechanism

Judy Chou 1

Affiliations

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

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Abstract

Event

UEG Week Berlin 2025

Topics

IBD Primary Care Surgery

Session

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

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

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Peter Irving

Fistulising Crohn's disease: Underlying mechanism

Judy Chou

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)

Severine Vermeire

Appendectomy? The solution for ulcerative colitis

Eva Visser

The pregnant IBD patient (Complete Session)

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.

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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

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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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Appendectomy? The solution for ulcerative colitis

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Appendectomy? The solution for ulcerative colitis

Eva Visser 1

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

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

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Summary

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Download PDF

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Thanks for your feedback.

Abstract

Event

UEG Week Berlin 2025

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Session

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Citation

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