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Introduction

Guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, is highly efficacious in participants (pts) with Crohn’s disease (CD) after intravenous (IV) or subcutaneous (SC) induction followed by SC maintenance. This analysis characterized pharmacokinetics (PK) and exposure-response (E-R) for efficacy and safety of both administration routes and confirmed assumptions for the development of IV and SC induction formulations.

Aims & Methods

GUS efficacy and safety in pts with moderate to severely active CD were evaluated in the phase 2 GALAXI 1 (200, 600, or 1200 mg IV at week [W]0, W4, and W8),¹ phase 3 GALAXI 2 and 3 (200 mg IV at W0, W4, and W8),² and phase 3 GRAVITI studies (400 mg SC at W0, W4, and W8).³ All studies used treat-through designs and the same SC maintenance dose regimens (100 mg q8w or 200 mg q4w). With an estimated ~50% bioavailability of SC GUS, the 2-fold higher SC induction dose was predicted to provide similar overall exposure and noninferior trough concentrations compared with the IV dose.
To characterize GUS PK, a population PK model was used to simulate exposure metrics for IV and SC induction using individual post-hoc PK parameters and actual pt dosages. Relationships between GUS exposure and select efficacy endpoints (clinical response, clinical remission, and endoscopic response) at week 12 were assessed.

Results

SC induction resulted in higher trough serum concentrations (at W12), lower peak serum concentrations, similar average concentrations (W0–W12), and similar area under the concentration-time curves (W0–W12) vs IV induction (Table). Regardless of induction route (IV or SC) or maintenance regimen, GUS serum concentrations reached steady state by W24.
W12 efficacy outcomes were comparable within GUS concentration quartiles after SC vs IV induction. Although pts with higher serum GUS concentrations tended to achieve greater W12 efficacy outcomes, this trend was no longer evident after accounting for a pt’s drug clearance or the half-life of the drug. W48 outcomes were similar in pts who received the same maintenance regimen, regardless of induction dose route. No positive E-R trends were seen between peak concentration and W12 efficacy endpoints; thus, the higher peak concentration observed with IV induction did not seem to improve efficacy. Across concentration quartiles, the incidence of safety events was comparable between pts who received GUS IV or SC induction regimens. No positive associations between serum concentrations and adverse events (infections, serious infections, and serious adverse events) or abnormal liver function tests were observed.

	GUS 200 mg IV q4w (N=622)	GUS 400 mg SC q4w (N=229)
C_max(µg/mL) Mean (SD)	70.1 (25.1)	27.7 (9.06)
C_{ave, week 0-12}(µg/mL) Mean (SD)	21.4 (7.06)	18.9 (6.47)
C_{trough, week 12}(µg/mL) Mean (SD)	9.76 (5.38)	14.7 (6.65)
AUC_{week 0-12}(day*µg/mL) Mean (SD)	1,800 (593)	1,590 (543)
AUC_{week 0-12}=area under the concentration-time curve from week 0 to week 12 (induction); C_{ave, week 0-12}=average concentration from week 0 to week 12 (induction); C_max=maximum concentration; C_{trough, week 12}=trough concentration at week 12 (induction); IV=intravenous; PK=pharmacokinetic; q4w=every 4 weeks; SC=subcutaneous; SD=standard deviation; W=week.

Conclusion

Average serum GUS concentrations and E-R relationships were similar after IV vs SC induction and had no impact on safety, supporting the use of either administration route and induction dose regimen in CD patients.

References

1. Sandborn WJ, et al. Guselkumab for the treatment of Crohn's disease: induction results from the phase 2 GALAXI-1 study. Gastroenterology. 2022; 162(6):1650-1664.e8.
2. Panaccione R, et al. Efficacy and safety of guselkumab therapy in patients with moderately to severely active Crohn’s disease: results of the GALAXI 2 & 3 phase 3 studies. Gastroenterology. 2024; 166 (5 Supplement):1057b.
3. Hart A, et al. Efficacy and safety of guselkumab subcutaneous induction and maintenance in participants with moderately to severely active Crohn's disease: results from the phase 3 GRAVITI study. Gastroenterology. 2025; S0016-5085(25)00522-0.

Disclosure

Geert D’Haens has served as advisor and/or speaker for Abbvie, Abivax, Agomab, Alimentiv, Anaptys Bio, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Galapagos, Glaxo Smith Kline, Index Pharmaceuticals, Johnson and Johnson, Merck, Polpharm, Prometheus biosciences, Sanofi, Takeda, Tillotts.
Omoniyi J. Adedokun, Tae Eun Yang, Nat A. Terry, Mobolaji Olurinde, Rian Van Rampelbergh, and Marion L. Vetter are employees of Janssen Research & Development (a Johnson & Johnson Company) and may own company stock/stock options.
Bruce E. Sands reports potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutics, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey, Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biotherapeutics, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, TR1X, Union Therapeutics and Ventyx Biosciences.
Silvio Danese reports potential conflicts of interest with 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.
Tadakazu Hisamatsu reports potential conflicts of interest with AbbVie, Bristol Myers Squibb, Daiichi-Sankyo, EA Pharma Co, Ltd., Eli Lilly, Gilead Sciences, Janssen Research & Development, LLC., JIMRO, Kissei Pharmaceutical Co, Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co., Ltd.
Remo Panaccione reports potential conflicts of interest with Abbivax, Abbott, AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB.

GUSELKUMAB PHARMACOKINETICS AND EXPOSURE-RESPONSE RELATIONSHIPS ARE CONSISTENT FOLLOWING INTRAVENOUS VERSUS SUBCUTANEOUS INDUCTION IN PARTICIPANTS WITH CROHN’S DISEASE

Geert R. D'Haens 1, Joseph Adedokun 2, Tae Eun Yang 2, Bruce E. Sands 3, Silvio Danese 4, Natalie Terry 2, Mobolaji Olurinde 2, Rian Van Rampelbergh 5, Marion Vetter 2, Tadakazu Hisamatsu 6, Remo Panaccione 7

1 Amsterdam University Medical Centers, Amsterdam, Netherlands

2 Janssen R&D, LLC., Spring House, United States

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

4 IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy

5 Janssen R&D, Antwerp, Belgium

6 Kyorin University School of Medicine, Tokyo, Japan

7 University of Calgary, Calgary, Canada

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

New treatments on the horizon for Crohn's disease (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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PEGOZAFERMIN DEMONSTRATED ROBUST HISTOLOGICAL IMPROVEMENT AND BENEFIT IN HEPATIC AND METABOLIC BIOMARKERS: RESULTS FROM A 48-WEEK MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2B TRIAL (ENLIVEN)

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Introduction

Metabolic dysfunction-associated steatohepatitis (MASH) is often associated with metabolic disorders such as obesity, metabolic syndrome, and/or diabetes. FGF21 analogs are promising therapies for MASH due to their direct anti-fibrotic effects as well as additional hepatic and extrahepatic benefits. Pegozafermin (PGZ), an FGF21 analog, was evaluated for safety and efficacy in a Phase 2b trial (ENLIVEN) with either weekly (QW) or every two-week (Q2W) dosing versus matching placebo in MASH patients with biopsy-proven F2/F3 fibrosis. Primary histology endpoints and non-invasive tests (NITs) were assessed at week 24, followed by additional NIT evaluation at the end of a 24-week blinded extension for a total of 48 weeks.

Aims & Methods

Patients were randomized to PGZ 15mg QW, 30mg QW, or 44mg Q2W or placebo for 24 weeks (histology-based primary endpoints). During the 24-week extension, most patients continued their assigned treatment with the exception of a subset of placebo patients who were re-randomized to receive PGZ 30mg QW. The full analysis set includes F2/F3 patients with NAFLD activity score (NAS) ≥4 at baseline (n=192).

Results

At 24-weeks, PGZ 30mg QW or 44mg Q2W led to statistically significant and clinical meaningful improvement in both primary histological endpoints (one stage of fibrosis improvement without worsening of MASH and MASH resolution without worsening of fibrosis) compared to placebo. Non-invasive testing at weeks 24 and 48 demonstrated that PGZ treatment was associated with robust and sustained reductions in liver fat content (MRI-PDFF), biomarkers of fibrosis (VCTE, ELF, PRO-C3) and liver injury (ALT, AST). PGZ also improved metabolic parameters such as lipids and HbA1c at both 24 and 48 weeks. PGZ was generally safe and well tolerated with the most common treatment emergent adverse events (TEAEs) being mild/moderate nausea and diarrhea. No deaths occurred; six early terminations for TEAEs including one drug-related serious AE occurred.

Conclusion

At 24 weeks, treatment with PGZ in MASH patients with F2/F3 fibrosis led to significant fibrosis regression and MASH resolution, which was corroborated by improvement across a variety of non-invasive tests including liver fat, inflammation, fibrosis, and metabolic markers. Benefits on NITs were sustained over the full 48-weeks of the study, with favorable safety and tolerability. PGZ is the first therapy to achieve fibrosis regression and MASH resolution with a Q2W dosing regimen. Phase 3 studies in noncirrhotic (ENLIGHTEN-Fibrosis) and cirrhotic (ENLIGHTEN-cirrhosis) patients are currently underway to confirm these results.

Disclosure

Jörn Schattenberg: Consultant: Akero, Alentis Therapeutics, Astra Zeneca, 89Bio, Boehringer Ingelheim, GSK, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers; Speaker: Gilead Sciences, Advanz, Echosens, MedPublico GmbH; Grants: Boehringer Ingelheim, Siemens Healthcare GmbH; Stock Options: AGED diagnostics, Hepta Bio
Arun J Sanyal: Consulting: Genefit, Gilead, Malinckrodt, Pfizer, Salix, Boehringer Ingelheim, Novartis, Bristol Meyers Squibb, Merck, Hemoshear, Lilly, Novo Nordisk, Terns, Albireo, Jannsen, Poxel, 89bio, Siemens, AstraZeneca, NGM Bio, Amgen, Regeneron, Genentech, Alnylam, Roche, Madrigal, Inventiva, Covance, Prosciento, HistoIndex, PathAI; Grants: Gilead, Malinckrodt, Boehringer Ingelheim, Novartis, Bristol Meyers Squibb, Merck, Lilly, Novo Nordisk, Fractyl, Madrigal, Inventiva; Stock holder: Exhalenz, GenFit, Hemoshear, Durect, Indalo, NorthSea, Tiziana, Rivus
Naim Alkhouri: Research funding: 89Bio, AbbVie/Allergan, Akero, Better Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Corcept, DSM, Galectin, Genentech, Genfit, Gilead, Hepagene, Healio, Intercept, Inventiva, Ionis, Madrigal, Merck, NGM, Noom, NorthSea, Novo Nordisk, Perspectum, Pfizer, Poxel, Viking, and Zydus; Speaker bureau: AbbVie/Allergan, Alexion, Echosens, Eisai, Exelixis, Gilead, Intercept, Perspectum, Salix, and Theratechnologies; Consultant: 89Bio, AbbVie/Allergan, Echosens, Fibronostics, Gilead, Intercept, Madrigal, Novo Nordisk, Perspectum, Pfizer, and Zydus.
Rohit Loomba: Consultant: Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Boston Pharmaceuticals, Bristol-Meyers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse Bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89bio, Terns Pharmaceuticals and Viking Therapeutics; Grants: Arrowhead Pharmacetuicals, AstraZeneca, Boegringer-Ingelheim, Bristol-Meyers Squibb, Eli Lilly, Galectin Therapeutics, Galmeed Pharmaceuticals, Gilead, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Pfizer, Sonic Incytes and Terns Pharmaceuticals; Stockholder: Co-founder LipoNexus, Inc
Mildred D Gottwald, Shibao Feng, Germaine D Agollah, Cynthia L Hartsfield, Hank Mansbach, Maya Margalit: 89bio employee and stock holder

PEGOZAFERMIN DEMONSTRATED ROBUST HISTOLOGICAL IMPROVEMENT AND BENEFIT IN HEPATIC AND METABOLIC BIOMARKERS: RESULTS FROM A 48-WEEK MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2B TRIAL (ENLIVEN)

Jörn Schattenberg 1, Arun J Sanyal 2, Naim Alkhouri 3, Mildred D. Gottwald 4, Shibao Feng 4, Germaine D. Agollah 4, Cynthia L Hartsfield 4, Hank Mansbach 4, Maya Margalit 5, Rohit Loomba 6

1 Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg, Germany

2 Virginia Commonwealth University School of Medicine, Richmond, United States

3 Arizona Liver Health, Phoenix, United States

4 89bio, San Francisco, United States

5 89bio, Rehovot, Israel

6 University of California San Diego MASLD Research Center, San Diego, United States

Event

UEG Week Berlin 2025

Topics

Hepatobiliary

Submission format

Abstract

Session

Lifestyle management and therapy in MASLD

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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RANDOMIZED CONTROLLED TRIAL COMPARING ENDOSCOPIC BALLOON DILATION VERSUS ENDOSCOPIC STRICTUROTOMY FOR SHORT STRICTURES (&LT; 3 CM) RELATED TO CROHN’S DISEASE (THE BEST-CD TRIAL) (NCT05521867)

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Introduction

Although endoscopic balloon dilation (EBD) remains the standard intervention for Crohn’s disease (CD)-associated strictures, its efficacy is limited by high recurrence and surgery rates. Retrospective analyses suggest endoscopic stricturotomy (ES) may offer superior outcomes, particularly in anastomotic strictures. However, no randomized trials have directly compared EBD and ES for short CD-related strictures.

Aims & Methods

This single-center, randomized controlled trial (August 2022–March 2025) enrolled adult CD patients (18–65 years) with symptomatic, predominantly fibrotic or mixed, short strictures (<3 cm), including both de novo and anastomotic types, accessible via standard endoscopy. Patients with multiple (>2) strictures, strictures beyond endoscopic reach, or prior stricturotomy were excluded. Participants were randomized to undergo either EBD or ES. The primary outcome was clinical recurrence at 1 year. Secondary outcomes included re-intervention, surgery, emergency visits, hospitalization, technical success, and adverse events.

Results

Out of 70 randomized patients, 69 were analyzed (EBD: 35; ES: 34). Baseline characteristics were comparable between groups. Technical success was similar (EBD: 91.4%, ES: 94.1%). On time to event analysis, clinical recurrence was significantly lower in the ES group (OR=0.343, 95% CI: 0.134–0.881; p=0.026). Re-intervention rates favored ES (EBD: 25.7%, ES: 8.8%; OR=0.337, 95% CI: 0.131–0.870; p=0.025). Surgery rates were numerically lower with ES (EBD: 11.4%, ES: 5.9%) but not statistically significant (p=0.581). Hospitalization was significantly more frequent in the EBD arm (OR=0.276, 95% CI: 0.091–0.840; p=0.023). ED visits also trended lower with ES, though not statistically significant (p=0.062) (see table). Adverse events occurred in 25.7% of EBD patients (bleeding n=3 [1 hemoclip], pain with admission n=3, micro-perforation n=1, post-procedure pain n=2) and 14.7% of ES patients (bleeding n=3 [1 self-limited, 1 coagrasper, 1 hemoclip], none required transfusion, suspected perforation n=1, mild pain n=1).

Outcome	EBD (n=35)	ES (n=34)	p-value	Odds Ratio (95% CI)
Technical Success (%)	91.4% (32/35)	94.1% (32/34)	0.70	-
Clinical Recurrence (%)	48.6%	23.5%	0.026	0.343 (0.134–0.881)
Re-intervention Rate (%)	25.7%	8.8%	0.025	0.337 (0.131–0.870)
Surgery (%)	11.4%	5.9%	0.581	0.707 (0.207–2.422)
Stricture-related ED Visits (%)	20.0%	11.8%	0.062	0.404 (0.156–1.047)
Stricture-related Hospitalizations (%)	25.7%	8.8%	0.023	0.276 (0.091–0.840)
Any Adverse Event (%)	25.7% (9/35)	14.7% (5/34)	0.45	-

Conclusion

In this interim analysis, ES was associated with significantly lower clinical recurrence, re-intervention, and hospitalization compared to EBD for short CD-related strictures, with similar safety outcomes. These findings support ES as a potentially superior first-line endoscopic strategy over EBD in selected patients with Crohn’s disease strictures. (NCT05521867)

References

Lan N, Shen B. Endoscopic Stricturotomy Versus Balloon Dilation in the Treatment of Anastomotic Strictures in Crohn's Disease. Inflamm Bowel Dis. 2018 Mar 19;24(4):897-907. doi: 10.1093/ibd/izx085. PMID: 29546384.

RANDOMIZED CONTROLLED TRIAL COMPARING ENDOSCOPIC BALLOON DILATION VERSUS ENDOSCOPIC STRICTUROTOMY FOR SHORT STRICTURES (&LT; 3 CM) RELATED TO CROHN’S DISEASE (THE BEST-CD TRIAL) (NCT05521867)

Partha Pal 1, Kanapuram Pooja 1, Rajesh Gupta 1, Manu Tandan 1, D. Nageshwar Reddy 1

1 Asian Institute of Gastroenterology, Hyderabad, India

Event

UEG Week Berlin 2025

Topics

Endoscopy Radiology & Imaging IBD

Submission format

Abstract

Session

Advances in the investigation of the small bowel

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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Optimising surgical therapies in fistulising Crohn's disease

Philip J. Tozer 1

1 St Marks Hospital, London, United Kingdom

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine Surgery

Session

Focus on fistulising Crohn’s disease

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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IS LIGHT TO MODERATE ALCOHOL DRINKING PROSPECTIVELY ASSOCIATED WITH THE ONSET OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE?

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Introduction

Updated nomenclature for steatotic liver disease (SLD) uses moderate-to-heavy alcohol drinking to classify metabolic dysfunction-associated steatotic liver disease (MASLD) and with increased alcohol intake (MetALD). However, the association between light-to-moderate alcohol drinking (≤14 g/d for females and ≤28 g/d for males) and the risk of SLD, particularly MASLD, remains unclear, with this knowledge gap being especially pronounced in Chinese populations where prospective cohort evidence remains scarce. In this study, we conducted a cohort study of 2942 Chinese adult participants using data from the Anhui Liver Disease Study (ALDS), where SLD and its subtypes were defined based on vibration-controlled transient elastography (VCTE).We examined the relationship between light-to-moderate alcohol drinking and the risk of SLD and MASLD.We further investigated gut microbiome changes linked to light-to-moderate drinking, and assessed the association between light-to-moderate alcohol-associated microbiota and SLD in a subset of the ALDS.

Aims & Methods

We aimed to investigate the association between light-to-moderate drinking and the risk of incident SLD/MASLD, assess the 1-year gut microbiome changes linked to light-to-moderate drinking, and examine the association between light-to-moderate alcohol-associated microbiota and SLD.In a cohort of 2942 Chinese adults from the Anhui Liver Disease Study (ALDS), alcohol intake was measured via a validated food frequency questionnaire, while SLD were diagnosed by vibration-controlled transient elastography. In a subset of ALDS (n=330), dietary information and fecal samples for 16S rRNA sequencing were collected twice, 1 year apart. Cox regression and logistic regression were used to calculate multivariable-adjusted hazard ratios (aHRs) and odds ratios (aORs) with 95%CIs, respectively.

Results

Upon 4 years of follow-up, 513 SLD (473 MASLD) were newly identified among participants without pre-existing SLD. Light-to-moderate alcohol drinkers exhibited higher risks of SLD (aHR=1.27, 95%CI: 1.03-1.58) and MASLD (aHR=1.27, 95%CI: 1.01-1.59) versus abstainers. Such positive association persisted in subgroups by age, sex, the number of cardiometabolic risk factors, physical activity, and diet quality. Beverage-specific analysis revealed positive associations with SLD risk for liquor (aHR=1.29, 95%CI:1.01-1.65) and beer (aHR=1.38, 95%CI: 0.96-1.99), but not wine. Longitudinal microbiome analysis identified 16 genera with altered abundance in light-to-moderate alcohol drinkers: 8 increased (including Actinomyces) and 8 decreased (all P_FDR<0.05). Among these genera, Actinomyces abundance correlated with SLD risk (aOR=1.19, 95%CI: 1.03-1.41).

Conclusion

Our findings support that light-to-moderate alcohol drinking was associated with higher risks of SLD and MASLD, which might be partly via modulation of gut microbial composition.

References

[1] Israelsen M, Francque S, Tsochatzis EA, Krag A. Steatotic liver disease. Lancet. 2024;404(10464):1761-78. https://doi.org/10.1016/S0140-6736(24)01811-7.
[2] Younossi ZM, Stepanova M, Ong J, Trimble G, AlQahtani S, Younossi I, Ahmed A, Racila A, Henry L. Nonalcoholic Steatohepatitis Is the Most Rapidly Increasing Indication for Liver Transplantation in the United States. Clin Gastroenterol Hepatol. 2021;19(3):580-9 e5. https://doi.org/10.1016/j.cgh.2020.05.064.
[3] Wong VWS, Ratziu V, Bugianesi E, Francque S, Zelber-Sagi S, Valenti L, Roden M, Schick F, Yki-Järvinen H, Gastaldelli A, Vettor R, Frühbeck G, Dicker D, Easl, Easl, Easd, Easo. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024;81(3):492-542. https://doi.org/10.1016/j.jhep.2024.04.031.
[4] Mak LY, Liu K, Chirapongsathorn S, Yew KC, Tamaki N, Rajaram RB, Panlilio MT, Lui R, Lee HW, Lai JC, Kulkarni AV, Premkumar M, Lesmana CRA, Hsu YC, Huang DQ. Liver diseases and hepatocellular carcinoma in the Asia-Pacific region: burden, trends, challenges and future directions. Nat Rev Gastroenterol Hepatol. 2024;21(12):834-51. https://doi.org/10.1038/s41575-024-00967-4.

IS LIGHT TO MODERATE ALCOHOL DRINKING PROSPECTIVELY ASSOCIATED WITH THE ONSET OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE?

Jie Chen 1, Yangxin Xu 1, Yu Chang 1, Qin Xinsheng 1, Hongjuan Cao 2, Zhuang Zhang 1, Wanshui Yang 1

1 Anhui Medical University, Hefei, China

2 Lu'an Municipal Center for Disease Control and Prevention, Lu'an, China

Event

UEG Week Berlin 2025

Topics

Hepatobiliary

Submission format

Abstract

Session

Lifestyle management and therapy in MASLD

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Poster

Audio / Video Poster

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Introduction

Tulisokibart, a TL1A monoclonal antibody, has demonstrated significantly higher rates of clinical remission and endoscopic and histologic improvements vs. placebo in participants with moderately to severely active ulcerative colitis (UC) in the ARTEMIS-UC clinical trial ¹. Although histologic remission has been associated with improved long-term outcomes in UC, histology is inconsistently performed and heterogeneously evaluated in routine clinical care as an assessment of remission depth.

Aims & Methods

This analysis of ARTEMIS-UC explores the correlation between changes in clinical, biomarker, endoscopic, and histologic endpoints following tulisokibart treatment over 50 weeks, potentially providing additional accessible indicators of treatment efficacy. ARTEMIS-UC enrolled two cohorts based on a genetic diagnostic test (Dx) for anti-TL1A treatment response: Cohort 1 (participants regardless of Dx results) and Cohort 2 (only Dx positive participants). We examined 15 relationships between five clinical, endoscopic, and biomarker endpoints and three histologic endpoints at Week 12 after induction (Cohort 1) and Week 50 (Cohorts 1 and 2) among induction responders continuing maintenance tulisokibart. Histologic endpoints included histologic improvement, histologic-endoscopic mucosal improvement (HEMI), and mucosal healing (Table) assessed in the Histology Analysis Set (HAS), i.e., participants who received ≥1 dose of study medication and had Geboes scores at both Baseline and Week 12. Clinical/endoscopic/biomarker endpoints included Modified Mayo Score for clinical remission, clinical response, endoscopic improvement, normalization of fecal calprotectin, and hsCRP normalization. The Phi correlation coefficient assessed pairwise correlations between clinical/endoscopic/biomarker and histologic endpoints.

Results

There were 65 and 34 tulisokibart participants included in the HAS population for the Week 12 and Week 50 analyses, respectively. The strongest correlations were the following: endoscopic improvement:HEMI, endoscopic improvement:mucosal healing, clinical remission:HEMI, and clinical remission:mucosal healing, all >0.8 at Week 12 (post-induction in Cohort 1) and >0.9 at Week 50 (post-maintenance dosing in Cohorts 1 and 2). Normalization of fecal calprotectin also demonstrated a strong correlation with histologic endpoints (>0.7) at Week 50 (Table).

Table: Correlation between Clinical and Histologic Endpoints

	Cohort 1 HAS Week 12			Cohort 1+2 HAS Week 50
Clinical Endpoints	Histologic Improvement^a	HEMI^b	Mucosal Healing^c	Histologic Improvement^a	HEMI^b	Mucosal Healing^c
hsCRP Normalization	0.19	-0.06	-0.06	0.15	0.36	0.36
Fecal Calprotectin Normalization	0.35	0.49	0.49	0.31	0.75	0.75
Clinical Response	0.34	0.41	0.41	0.25	0.42	0.42
Endoscopic Improvement	0.57	0.87*	0.87*	0.57	0.94**	0.94**
Clinical Remission	0.60	0.85*	0.85*	0.61	0.94**	0.94**
HAS = Histology Analysis Set (participants who received ≥1 dose of study medication and had Geboes scores at both Baseline and Week 12) Bold = correlation > 0.7; bold and = correlation > 0.8; bold and * = correlation > 0.9; higher values indicate greater correlation between endpoints Correlation is phi correlation for two dichotomized variables ^aGeboes score ≤ 3.1; ^b Geboes score ≤ 3.1 and endoscopy subscore ≤ 1 without friability; ^c Geboes score ≤ 2B.1 and endoscopy subscore ≤ 1 without friability

Conclusion

Strong correlations exist between clinical, endoscopic, and histologic endpoints after 12 weeks of induction therapy with tulisokibart, followed by 38 weeks of maintenance therapy in induction responders. These findings underscore the potential for clinical remission to reflect both endoscopic and histologic healing in UC patients, which may enhance patient management strategies and enable a more comprehensive understanding of treatment efficacy. Moreover, these findings indicate the potential of tulisokibart in achieving deep remission² in patients with ulcerative colitis.

References

1) Sands BE et al. N Engl J Med. 2024 ;391:1119-1129; 2) Lobatón T et al. United European Gastroenterol J. 2018;6:765-772.

Disclosure

The submitting author of an abstract is requested to declare any potential conflict of interest for all authors during the abstract submission. Moreover, the authors’ names (full first names, family names), gender and affiliation (places of work/institution, city, country) must be provided.
CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), Roche, Sanofi, Takeda, Tillotts Pharma; speaker’s fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Ferring, Pfizer
RWL discloses advisory board membership: AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Takeda; research grant recipient: Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant, McKusker Charitable Foundation.
JL reports no financial competing interests
XH reports support from AbbVie, Abivax, Alphasigma, Arena, Cellgen, Gilead, Eli Lilly, Enterome, Janssen, InDex Pharmaceuticals, Pfizer, MSD, Roche, Salix, Sangamo, Takeda, and Theravance for clinical research; consulting fees from AbbVie, Abivax, Arena, Galapagos, Gilead, Janssen, Pfizer, Roche, Sangamo, Takeda, and Viatris; and lecture fees from AbbVie, Abivax, Amgen, Arena, Galapagos, Gilead, Fresenius-Kabi, Janssen, Pfizer, Roche, Sangamo, Takeda, and Mylan.
Brigid S. Boland: BSB has research grants from MSD, Mirador, Gilead as well as serves as a consultant for Abbvie, MSD, Celltrion.
JX, WZ, and MY are employees of MSD.