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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 1,2, Simon Mark Dahl Baunwall 1, Cynthia Seow 3, Dana Duricova 4, Sunanda Kane 5, Neha Zacharias 6, Rupert W Leong 7,8, Bel Klaartje Kok 9, Anna Kagramanova 10,11, Barbora Pipek 12,13, Kristina Candido 14, Rachel Cooney 15, Rafal Filip 16,17, Vytautas Kiudelis 18, Michal Konecny 19, Daniela Pugliese 20,21, Genoile Silva 22, Edoardo Vincenzo Savarino 23, Brigita Smolovic 24, Sophie Vieujean 25, Shu-Chen Wei 26, Uma Mahadevan 27

Affiliations

1 Aarhus University Hospital, Aarhus N, Denmark

2 Aarhus University, 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

8 Macquarie University, Sydney, Australia

9 Barts Health NHS Trust, London, United Kingdom

10 A. S. Loginov Moscow Clinical Scientific Center, Moscow, Balaschiha, Russian Federation

11 Research Institute of Health Organization and Medical Management, Moscow, Russian Federation

12 Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, Czechia

13 Hospital AGEL Vitkovice, Ostrava, Czechia

14 McGill University, Montreal, Canada

15 University Hospital Birmingham NHS Trust, Birmingham, United Kingdom

16 Regional Hospital No. 2 in Rzeszow, Rzeszów, Poland

17 University of Rzeszow, Rzeszow, Poland

18 Lithuanian University of Health Sciences, Kaunas, Lithuania

19 Palacky University and University Hospital Olomouc, Olomouc, Czechia

20 Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy

21 Università Cattolica del Sacro Cuore, Rome, Italy

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

23 University of Padua, Division of Gastroenterology, Padua, Italy

24 Faculty of Medicine, University of Montenegro, Podgorica, Montenegro

25 University Hospital CHU of Liège, Liège, Belgium

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

27 University of California, San Francisco, United States

Summary

AI Generated

In a global multicenter retrospective study of 43 JAK inhibitor-exposed pregnancies in women with IBD, maternal complication rates were low and no congenital abnormalities were observed among 35 live births, with reassuring infant outcomes including normal development and no adverse vaccine responses.

Among 35 live births, no congenital abnormalities were reported, with 1 preterm infant (2.9%), 3 small for gestational age (8.6%), and 1 with Apgar score less than 7 at 5 minutes (2.9%).
Maternal complications were low with no cases of DVT or preeclampsia, though 3 cases of premature rupture of membranes (GA 34-37) and 4 hospitalizations for infection or other complications occurred.
Disease activity was present in 51.2% of pregnancies, and among women who discontinued JAK inhibitors in the first or second trimester, 63.6% experienced disease flare.
Follow-up of 31 infants (median 17 months, range 1-88) showed 100% normal development, with no adverse effects reported following live BCG, rotavirus, or MMR vaccines.
Two infants (6.5%) required hospitalization for infection at age 0-4 months, both born to mothers with moderate-to-severe disease activity treated with systemic corticosteroids and upadacitinib initiated during pregnancy, with no infection-related sequelae.
Among 24 breastfeeding women, 29.2% continued JAK inhibitor treatment during lactation.

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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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FERMENTABLE FIBER INTAKE AND REDUCED CROHN’S DISEASE RISK: INSIGHTS FROM THE GEM PROSPECTIVE COHORT

Williams Turpin

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Silvio Danese

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Judy Chou

UEG Presentation

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FERMENTABLE FIBER INTAKE AND REDUCED CROHN’S DISEASE RISK: INSIGHTS FROM THE GEM PROSPECTIVE COHORT

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FERMENTABLE FIBER INTAKE AND REDUCED CROHN’S DISEASE RISK: INSIGHTS FROM THE GEM PROSPECTIVE COHORT

Mingyue Xue 1, Catherine Mcshane 2, Kim Jeongseok 2, Haim Leibovitzh 3, Jingcheng Shao 2, Qilong Li 2, Karen Madsen 4, Reihane Khorasaniha 2, Anne Griffiths 5, Thomas D Walters 5, Allan Hillary Steinhart 1, Mark S. Silverberg 2, Levinus Dieleman 6, Hien Huynh 6, Remo Panaccione 7, Paul Beck 7, Guy Aumais 8, Iwona Wrobel 7, Alain Bitton 9, John K. Marshall 10, Charles N. Bernstein 11, Jeffrey Hyams 12, Paul Moayyedi 13, Sun-Ho Lee 2, Heather Armstrong 6, Ken Croitoru 14, Williams Turpin 2

Affiliations

1 Mount Sinai Hospital Dept. of Medicine, Toronto, Canada

2 Mount Sinai Hospital, Toronto, Canada

3 Mount-Sinai Hospital, Toronto, Toronto, Canada

4 University of Alberta, Alberta, Canada

5 Hospital for Sick Children, Toronto, Canada

6 University of Alberta Division of Gastroenterology Dept. of Medicine, Edmonton, Canada

7 University of Calgary, Calgary, Canada

8 University of Montreal / Maisonneuve Hospital, Montreal, QC, Canada

9 Royal Victoria Hospital Dept. of Gastroenterology, Montreal, Canada

10 McMaster University, Burlington, Canada

11 University of Manitoba, Winnipeg, Canada

12 CT Children's, Hartford, United States

13 McMaster University Dept. of Medicine Dept. of Gastroenterology - McMaster University Dept. of Medic, Hamilton, Canada

14 Mt Sinai Hospital, Toronto, Canada

Summary

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Abstract

Introduction

The cause of Crohn’s Disease (CD) remains unclear; however evidence suggests that dietary factors play a key role. With a rising incidence and no definitive cure, identifying modifiable risk factors is critical in preventing CD development. We aimed to study the association between fermentable dietary fibre intake and the future development of CD in an at-risk population.

Aims & Methods

Participants were recruited as part of the Crohn’s and Colitis Canada GEM study, a prospective cohort study of healthy first-degree relatives of patients with CD. At enrolment, a validated food frequency questionnaire was administered. Pectin, β-glucan, inulin, fructooligosaccharides (FOS), and arabinoxylan intake were quantified, and values energy-adjusted. Survival analysis was used to test the association between intake of fibre subtypes and risk of CD development. Generalized estimating equation tested the association between fibre intake and baseline impaired intestinal permeability (fractional urinary excretion of lactulose to mannitol ratio (LMR) >0.025); subclinical gut inflammation (faecal calprotectin (FCP) >250 μg/g); and faecal microbiome composition via 16s rRNA sequencing.

Results

76 of the 2,659 participants developed CD with a median follow-up of 8.9 years (IQR=5.7-12.3). Median age at recruitment was 17 years (IQR=12-25). 47% were male. Higher intake of inulin (HR = 0.78; 95% CI=0.61–0.99; p=0.04) and β-glucan (HR = 0.78; 95% CI=0.61–0.99; p=0.04) were associated with a reduced risk of CD development. No fibre subtype was associated with a higher risk of CD development. Lower intake of pectin, inulin, FOS and β-glucan was associated with impaired intestinal permeability (0.005<p<0.04). Lower inulin intake was associated with high FCP levels (p = 0.046). Higher pectin intake was associated with increased alpha diversity of faecal microbiome (p = 0.028). Higher inulin, FOS and pectin intake was associated with a shift in microbial taxa previously shown to be protective against CD onset in the GEM cohort; a reduction in Ruminococcus torques and an increase in NK4A214 group (phylum Firmicutes) presence (3.25×10⁻¹⁰<q<0.04).

Conclusion

This study demonstrates that dietary intake of fermentable fibre subtypes is associated with a reduced risk of CD development as well as with pleiotropic changes in CD risk biomarkers including microbiome, intestinal permeability, and subclinical inflammation. This suggests that the potential benefit of fermentable fibres on CD risk may involve changes in barrier function, and microbiome composition and function. Targeted interventions based on these findings could prove effective in preventing the onset of CD.

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

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Williams Turpin

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Oshrit Hoffer

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Eva Visser

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Britta Siegmund

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Silvio Danese

Fistulising Crohn's disease: Underlying mechanism

Judy Chou

UEG Presentation

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

TRANSFORMING IUS INTERPRETATION: INTEGRATION OF AI MODELS IN INTESTINAL ULTRASOUND IMAGING

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TRANSFORMING IUS INTERPRETATION: INTEGRATION OF AI MODELS IN INTESTINAL ULTRASOUND IMAGING

Dan Carter 1, Gal Ashkenzai 2, Oshrit Hoffer 2

Affiliations

1 Sheba Medical Center, Ramat Gan, Israel

2 Afeka Colledge of Engineering, Tel Aviv, Israel

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Abstract

Introduction

Accurate diagnosis and monitoring of inflammatory bowel diseases (IBD) are essential for effective management and reduction of complications. Intestinal ultrasound (IUS) is a non-invasive and cost-effective imaging modality for IBD assessment, yet its widespread adoption is limited by operator dependency and interobserver variability. Artificial intelligence (AI) offers the potential to overcome these limitations by improving diagnostic accuracy and standardizing interpretation.

Aims & Methods

This study aimed to develop an AI-assisted model for the automatic detection of active inflammation in IUS images, using bowel wall thickness (BWT) as a key marker. We further aimed to create an automatic tool for detecting bowel segments within ultrasound images and to extend its application from single images to cine loops. Grayscale ultrasound images and cine-loops of the terminal ileum were collected from Crohn’s disease patients undergoing IUS at a tertiary center. The dataset included both normal and abnormal BWT and was annotated by an experienced operator. Preprocessing involved anonymization and normalization. Automated segmentation algorithms were used to isolate bowel wall structures, and deep learning techniques, including convolutional neural networks (CNNs) and YOLO (You Only Look Once) object detection, were employed to analyze the images.

Results

The study included 2,735 grayscale ultrasound images and cine-loops of the terminal ileum from patients with Crohn's disease. The dataset was divided into three sets: a training set of 1980 images, a validation set of 220 images, and a test set of 515 images. Our model achieved robust performance metrics, including sensitivity, specificity, and accuracy of 99.1%, 94.6%, and 91.5%, respectively, for BWT detection, with an area under the receiver operating characteristic curve (AUC) of 0.85. Our model was validated on 10 independent cine-loops, comprising 7 abnormal and 3 normal cases. It accurately identified bowel wall thickening (BWT) in all seven abnormal cases, correctly classifying them as abnormal. Additionally, the model successfully confirmed the absence of BWT in all three normal cine-loops, categorizing them appropriately as normal.

Conclusion

This study represents a significant advancement in the application of artificial intelligence to intestinal ultrasound interpretation by integrating automated segmentation, automatic analysis capabilities, and cine-loop evaluation. Our model extends beyond traditional static image analysis, paving the way for real-time and dynamic assessments of bowel inflammation. This approach highlights the potential of our AI tools to reduce operator dependency, improve diagnostic accuracy, and enhance clinical workflows, making IUS more accessible and reliable for clinicians with varying levels of expertise.

Disclosure

Prof. Dan Carter has received speaker’s fees, research support, or consultancy fees from Takeda, Janssen, AbbVie, and Taro

Event

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

Artificial intelligence in IBD

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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FERMENTABLE FIBER INTAKE AND REDUCED CROHN’S DISEASE RISK: INSIGHTS FROM THE GEM PROSPECTIVE COHORT

Williams Turpin

TRANSFORMING IUS INTERPRETATION: INTEGRATION OF AI MODELS IN INTESTINAL ULTRASOUND IMAGING

Oshrit Hoffer

Appendectomy? The solution for ulcerative colitis

Eva Visser

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

Britta Siegmund

EFFICACY AND SAFETY OF SUBCUTANEOUS GUSELKUMAB INDUCTION AND MAINTENANCE THERAPY IN PARTICIPANTS WITH ULCERATIVE COLITIS: RESULTS THROUGH WEEK 48 FROM THE PHASE 3 ASTRO STUDY

Silvio Danese

Fistulising Crohn's disease: Underlying mechanism

Judy Chou

UEG Presentation

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

Appendectomy? The solution for ulcerative colitis

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Appendectomy? The solution for ulcerative colitis

Eva Visser 1

Affiliations

1 Amsterdam University Medical Centre, Amsterdam, Netherlands

Summary

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Abstract

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine Paediatrics Surgery

Session

What's new in ulcerative colitis 2025?

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

FERMENTABLE FIBER INTAKE AND REDUCED CROHN’S DISEASE RISK: INSIGHTS FROM THE GEM PROSPECTIVE COHORT

Williams Turpin

TRANSFORMING IUS INTERPRETATION: INTEGRATION OF AI MODELS IN INTESTINAL ULTRASOUND IMAGING

Oshrit Hoffer

Appendectomy? The solution for ulcerative colitis

Eva Visser

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

Britta Siegmund

EFFICACY AND SAFETY OF SUBCUTANEOUS GUSELKUMAB INDUCTION AND MAINTENANCE THERAPY IN PARTICIPANTS WITH ULCERATIVE COLITIS: RESULTS THROUGH WEEK 48 FROM THE PHASE 3 ASTRO STUDY

Silvio Danese

Fistulising Crohn's disease: Underlying mechanism

Judy Chou

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.

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

Britta Siegmund 1

Affiliations

1 Charité - Universitätsmedizin Berlin, Berlin, Germany

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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:

FERMENTABLE FIBER INTAKE AND REDUCED CROHN’S DISEASE RISK: INSIGHTS FROM THE GEM PROSPECTIVE COHORT

Williams Turpin

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Britta Siegmund

EFFICACY AND SAFETY OF SUBCUTANEOUS GUSELKUMAB INDUCTION AND MAINTENANCE THERAPY IN PARTICIPANTS WITH ULCERATIVE COLITIS: RESULTS THROUGH WEEK 48 FROM THE PHASE 3 ASTRO STUDY

Silvio Danese

Fistulising Crohn's disease: Underlying mechanism

Judy Chou

UEG Presentation

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

EFFICACY AND SAFETY OF SUBCUTANEOUS GUSELKUMAB INDUCTION AND MAINTENANCE THERAPY IN PARTICIPANTS WITH ULCERATIVE COLITIS: RESULTS THROUGH WEEK 48 FROM THE PHASE 3 ASTRO STUDY

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 SUBCUTANEOUS GUSELKUMAB INDUCTION AND MAINTENANCE THERAPY IN PARTICIPANTS WITH ULCERATIVE COLITIS: RESULTS THROUGH WEEK 48 FROM THE PHASE 3 ASTRO STUDY

Jessica Allegretti 1, Laurent Peyrin-Biroulet 2, Millie Long 3, Matthew Germinaro 4, Thomas Baker 4, Mary Kavalam 4, Yelina Alvarez 4, Karen Hertzog 4, Silke Jorgens 4, Hongyan Zhang 4, Lingjing Jiang 4, Tadakazu Hisamatsu 5, David T. Rubin 6, Silvio Danese 7

Affiliations

1 Brigham and Women´s Hospital, Boston, United States

2 Inserm U1256, Nancy University Hospital, Vandoeuvre-les-Nancy, France

3 University of North Carolina at Chapel hill, Chapel Hill, United States

4 Johnson & Johnson, Spring House, United States

5 Kyorin University School of Medicine, Tokyo, Japan

6 University of Chicago Medicine, Chicago, United States

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

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Abstract

Introduction

Guselkumab (GUS), a dual-acting interleukin-23p19 subunit inhibitor, demonstrated efficacy in participants (pts) with ulcerative colitis (UC) treated with intravenous (IV) or subcutaneous (SC) induction. Here, we report the efficacy and safety of SC induction followed by SC maintenance through Week (W) 48 in ASTRO, a phase 3, randomized, double-blind, placebo (PBO)-controlled, treat-through study in pts with moderately to severely active UC.

Aims & Methods

Eligible pts had modified Mayo scores of 5 to 9, rectal bleeding subscore of ≥1, and Mayo endoscopic subscore (MES) ≥2. Pts also had documented inadequate response/intolerance to biologics, Janus kinase (JAK) inhibitors, and/or sphingosine-1-phosphate (S1P) inhibitors (BIO/JAKi/S1Pi-IR) or to corticosteroids, 6-mercaptopurine, or azathioprine. Randomization was stratified by baseline BIO/JAKi/S1Pi-IR status and MES with 418 pts allocated 1:1:1 to GUS 400 mg SC every 4 weeks (q4w) (×3)→GUS 200 mg SC q4w (N=140), GUS 400 mg SC q4w (×3)→GUS 100 mg SC every 8 weeks (q8w) (N=139), or PBO SC (N=139). PBO pts who met rescue criteria were switched to GUS at W16; GUS pts who met rescue criteria stayed on their assigned GUS dose regimen (sham rescue).

Results

At W48, greater proportions of pts in the GUS groups achieved clinical remission compared with PBO (36.7% for GUS 100 mg q8w [Δ 29.5%], 42.9% for GUS 200 mg q4w [Δ 35.6%], 7.2% for PBO) (Table). Endoscopic remission proportions were 25.9% for GUS 100 mg q8w (Δ 20.9%), 26.4% for GUS 200 mg q4w (Δ 21.4%), and 5.0% for PBO. Clinical response, symptomatic remission, endoscopic improvement, histologic improvement, and histologic remission proportions were also greater for GUS vs PBO. Consistent with the results of the overall population, efficacy was also observed for subpopulations of BIO/JAKi/S1Pi-naïve and BIO/JAKi/S1Pi-IR pts. Safety events per 100 pts-years were not greater in the GUS groups compared with the PBO group: adverse events (AE) (GUS 100 mg q8w and 200 mg q4w vs PBO: 308.3 and 310.7 vs 357.1), serious AEs (6.5 and 8.2 vs 38.4), serious infections (0.8 and 2.5 vs 3.7), and AEs leading to treatment discontinuation (4.9 and 4.1 vs 19.8).
Table. Efficacy endpoints at Week 48 in the overall population and by biologic, JAK inhibitor, and/or S1P inhibitor history

	Overall			BIO/JAKi/S1Pi-naïve			BIO/JAKi/S1Pi-IR
Outcomes at Week 48	Placebo SC (N=139)	GUS 400 mg SC→ GUS 100 mg SC q8w (N=139)	GUS 400 mg SC→ GUS 200 mg SC q4w (N=140)	Placebo SC (N=79)	GUS 400 mg SC→ GUS 100 mg SC q8w (N=81)	GUS 400mg SC→ GUS 200mg SC q4w (N=83)	Placebo SC (N=56)	GUS 400 mg SC→ GUS 100 mg SC q8w (N=57)	GUS 400 mg SC→ GUS 200 mg SC q4w (N=55)
Clinical remission	10 (7.2)	51 (36.7) Δ 29.5 P<0.001	60 (42.9) Δ 35.6 P<0.001	6 (7.6)	39 (48.1) Δ 40.3 P<0.001	42 (50.6) Δ 43.0 P<0.001	4 (7.1)	12 (21.1) Δ 13.7 P=0.034	18 (32.7) Δ 25.2 P<0.001
Clinical response	26 (18.7)	78 (56.1) Δ 37.4 P<0.001	83 (59.3) Δ 40.6 P<0.001	19 (24.1)	52 (64.2) Δ 39.5 P<0.001	54 (65.1) Δ 40.8 P<0.001	7 (12.5)	25 (43.9) Δ 30.9 P<0.001	29 (52.7) Δ 39.3 P<0.001
Endoscopic improvement	16 (11.5)	62 (44.6) Δ 33.1 P<0.001	66 (47.1) Δ 35.6 P<0.001	10 (12.7)	46 (56.8) Δ 44.0 P<0.001	45 (54.2) Δ 41.7 P<0.001	6 (10.7)	16 (28.1) Δ 16.0 P=0.024	21 (38.2) Δ 26.8 P<0.001
Endoscopic remission	7 (5.0)	36 (25.9) Δ 20.9 P<0.001	37 (26.4) Δ 21.4 P<0.001	5 (6.3)	27 (33.3) Δ 26.9 P<0.001	28 (33.7) Δ 27.5 P<0.001	2 (3.6)	9 (15.8) Δ 11.5 P=0.033	9 (16.4) Δ 12.6 P=0.025
Symptomatic remission	20 (14.4)	66 (47.5) Δ 33.1 P<0.001	75 (53.6) Δ 39.2 P<0.001	15 (19.0)	47 (58.0) Δ 38.6 P<0.001	51 (61.4) Δ 42.3 P<0.001	5 (8.9)	19 (33.3) Δ 24.3 P=0.001	24 (43.6) Δ 34.0 P<0.001
Histologic improvement	18 (12.9)	65 (46.8) Δ 33.8 P<0.001	73 (52.1) Δ 39.2 P<0.001	13 (16.5)	45 (55.6) Δ 38.6 P<0.001	50 (60.2) Δ 43.8 P<0.001	4 (7.1)	20 (35.1) Δ 26.8 P<0.001	23 (41.8) Δ 34.1 P<0.001
Histologic remission	15 (10.8)	52 (37.4) Δ 26.6 P<0.001	63 (45.0) Δ 34.2 P<0.001	11 (13.9)	35 (43.2) Δ 29.1 P<0.001	41 (49.4) Δ 35.5 P<0.001	4 (7.1)	17 (29.8) Δ 21.5 P=0.002	22 (40.0) Δ 32.4 P<0.001
Data are presented as n (%); ∆% (adjusted treatment difference) versus placebo; nominal p-value versus placebo. The adjusted treatment difference was based on the common risk difference by use of the Mantel-Haenszel stratum weights and the Sato variance estimator. In the overall population, the p-values were based on the Mantel-Haenszel test, stratified by BIO/JAKi/S1Pi-IR status (Yes/No) and Mayo endoscopic subscore at baseline (Moderate [2]/Severe [3]). For the BIO/JAKi/S1Pi-naive/-IR subgroups, the p-values were stratified only by the Mayo endoscopic subscore at baseline. Participants who, prior to Week 48, had an ostomy or colectomy, a prohibited change in UC medications, discontinued study agent due to lack of efficacy or an AE of worsening of UC, or met rescue criteria per IWRS were considered not to have achieved any of the key efficacy endpoints shown at Week 48. For participants who discontinued study agent due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis, their observed values were used, if available. Participants who discontinued study agent prior to Week 48 due to other reasons were considered not to have achieved any of the efficacy endpoints shown at Week 48. Participants who were missing one or more of the components pertaining to an endpoint at Week 48 were considered not to have achieved the endpoint. Endpoint definitions: clinical remission, Mayo SFS 0/1 and not increased from BL, Mayo RBS=0, and MES 0/1 with no friability; clinical response, ≥30% and ≥2-point decrease from BL in Modified Mayo score with ≥1-point decrease from BL in RBS or RBS 0/1; endoscopic improvement, MES 0/1 with no friability; endoscopic remission, MES of 0; symptomatic remission, SFS 0/1 and not increased from BL and RBS=0; histologic improvement, neutrophil infiltration in <5% of crypts; no crypt destruction; and no erosions, ulcerations, or granulation tissue per Geboes grading system; histologic remission, absence of neutrophils from the mucosa (both lamina propria and epithelium); no crypt destruction; and no erosions, ulcerations, or granulation tissue per Geboes grading system. AE=adverse event; BIO=biologic; BL=baseline; COVID-19=coronavirus disease 2019; GUS=guselkumab; IR=inadequate response; IWRS=Interactive Web Response System; JAK=Janus kinase; JAKi=JAK inhibitor; MES=Mayo endoscopic subscore; N=population size; n=sample size; [HZ1] q4w=every 4 weeks; q8w=every 8 weeks; RBS=rectal bleeding subscore; S1P=sphingosine-1-phosphate; S1Pi=S1P inhibitor; SC=subcutaneous; SFS=stool frequency subscore; UC=ulcerative colitis

Conclusion

GUS SC induction followed by SC maintenance was efficacious through 1 year in pts with moderately to severely active UC, and the safety profile is consistent with GUS in its approved indications including UC.

Disclosure

ML reports research support from Lilly, Pfizer, and Takeda; consulting for AbbVie, Bristol Myers Squibb, Intercept, Janssen (Johnson & Johnson), Lilly, Pfizer, Prometheus, Roivant, Takeda, and Target RWE.
JRA reports grant support from Janssen, Merck, and Pfizer; consultancy fees from AbbVie, Adiso, Bristol Myers Squibb, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck, Pfizer, Roivant, Celltrion, TrexBio, Shattuck Labs and Seres Therapeutics; payments for speaking from AbbVie, Bristol Myers Squibb, and Janssen; and is a steering committee member and investigator for Janssen.
SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB, and Vifor; and reports lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
MG, TB, YA, KH, SJ, LJ, and HZ are employees of and may own stock in Johnson & Johnson.
TH reports research grants from AbbVie GK, Boston Scientific Corporation, EA Pharma Co. Ltd., JIMRO Co. Ltd., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Pfizer Inc., Takeda Pharmaceutical Co. Ltd., and Zeria Pharmaceutical Co. Ltd.; consulting fees from AbbVie GK, Abivax, Bristol Myers Squibb, EA Pharma Co. Ltd., Gilead Sciences, Janssen Pharmaceutical K.K., Lilly, Mitsubishi Tanabe Pharma Corporation, and Pfizer Inc.; and lecture fees from AbbVie GK, EA Pharma Co. Ltd., Janssen Pharmaceutical K.K., JIMRO Co., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co. Ltd.
DTR reports consulting and/or speaker fees and/or advisory board participation for AbbVie, Altrubio, Apex, Avalo, Bristol Myers Squibb, Buhlmann Diagnostics, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Janssen (Johnson & Johnson), Lilly, Pfizer, Samsung Neurologica, and Takeda; Altrubio, Datos Health, and Iterative Health stock options; grants from Takeda; and membership on the Board of Directors of Cornerstones Health, Inc. and on the Crohn’s & Colitis Foundation’s Board of Trustees.
LPB reports grants or contracts from Celltrion, Fresenius Kabi, Medac, MSD, and Takeda; consulting and/or payment or honoraria and/or data safety monitoring board or advisory board participation for AbbVie, Abivax, Adacyte, Alfasigma, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, Bristol Myers Squibb, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GlaxoSmithKline, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Kern Pharma, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, and Ysopia; and meeting attendance/travel support from AbbVie, Alfasigma, Amgen, Celltrion, Connect Biopharm, Ferring, Galapagos, Genentech, Gilead, Gossamer Bio, Janssen, Lilly, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer, and Tillots.

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine

Submission format

Abstract

Session

Advanced therapies in ulcerative colitis

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Fistulising Crohn's disease: Underlying mechanism

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Fistulising Crohn's disease: Underlying mechanism

Judy Chou 1

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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

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