UEG's educational platform for gastroenterology education bringing recordings, courses, guidelines, and more together in one place.

UEG Week Berlin 2025 Recordings Gut Guide online

Rate for better recommendations!

Your feedback helps us show you more of what you like and less of what you dislike!

More of this!

We will show you more similar content.

Not for me!

We won't suggest this again.

Bookmark!

Save this content for later!

New to myUEG? Create an account! Log In with myUEG account

UEG Poster

Standard Poster

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

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

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

COMPARATIVE SAFETY OF JANUS KINASE INHIBITORS VS. TUMOR NECROSIS FACTOR ANTAGONISTS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES

Dhruv Ahuja 1, Kuan-Hung Yeh 2, Han Hee Lee 3, Sagar B. Patel 2, Shane W. Goodwin 4, Christopher Ma 5, Ashwin N. Ananthakrishnan 6, Namrata Singh 7, Vipul Jairath 4, Ronghui Xu 8, Siddharth Singh 2

Affiliations

1 University of California, San Diego, USA; Indira Gandhi Hospital, New Delhi, San Diego, United States

2 University of California, San Diego, USA, San Diego, United States

3 Catholic University of Korea, Seoul, Korea, Republic of

4 Western University, London, Ontario, Canada, Ontario, Canada

5 University of Caglary, Calgary, Canada

6 Harvard Medical School, Boston, Massachusetts, USA, Boston, United States

7 University of Washington, Seattle, Washington, USA, Seattle, United States

8 University of California, San Diego, San Diego, United States

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

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

Abstract

Introduction

We conducted a retrospective cohort study comparing the safety of Janus kinase (JAK) inhibitors vs. tumor necrosis factor-a (TNF) antagonists in patients with inflammatory bowel diseases (IBD).

Aims & Methods

Using an administrative claims databasein the U.S, Optum Labs®, we identified patients with IBD who were new users of either JAK inhibitors or TNF antagonists between 2016-2023 and had insurance coverage for at least 1y before and after treatment initiation. We compared the risk of infections (overall, and serious infections requiring hospitalization), venous thromboembolism (VTE) and major adverse cardiovascular events (MACE) between patients treated with JAK inhibitors vs. TNF antagonists through stabilized inverse probability of treatment weighted (IPW) Cox proportional hazards model accounting for baseline disease characteristics, healthcare utilization, comorbidities, and medication exposure.

Results

We included 856 patients treated with JAK inhibitors (age, 47±17y; 82% with ulcerative colitis [UC]; 23% on upadacitinib) and 9422 patients treated with TNF antagonists (age, 45±18y, 44% with UC). JAK inhibitors were associated with higher risk of overall infections (incidence rate [IR], 62.4 per 100-py vs. 37.4 per 100-py; HR, 1.67 [95% CI, 1.44-1.93]), but not serious infections (IR, 4.9 vs. 5.4 per 100-py; HR, 1.02 [0.72-1.44]) compared with TNF antagonists. There was no difference in the risk of VTE (IR, 1.3 vs. 1.2 per 100-py; HR, 0.67 [0.35-1.29]). JAK inhibitors (vs. TNF antagonists) were associated with lower risk of MACE (IR, 0.4 vs. 0.7 per 100-py; HR, 0.37 [0.15-0.96]). Findings were largely stable on subgroup analyses based on type of IBD, type of JAK inhibitors, age and baseline risk of adverse events.

Table 1. Incidence rates and hazard ratios with JAK inhibitors and TNF antagonists in patients with Inflammatory bowel disease

Incidence rate per 100 person-years	Overall	JAK inhibitors	TNF antagonists
Overall Infections	38.95 [37.80; 40.09]	62.39 [56.49;68.29]	37.43 [36.27; 38.59]
Serious infections	5.34 [4.98; 5.69]	4.85 [3.55; 6.14]	5.37 [5.00; 5.74]
Venous thromboembolism	1.23 [1.06; 1.39]	1.32 [0.65; 1.99]	1.22 [1.05; 1.39]
Major adverse cardiovascular events	0.68 [0.55; 0.82]	0.44 [0.05; 0.82]	0.69 [0.56; 0.83]
Hazard ratios for JAK inhibitors vs. TNF antagonists	IBD	Crohn’s disease	Ulcerative colitis
Overall Infections	1.67 [1.44-1.93]	1.91 [1.47-2.48]	1.45 [1.29-1.64]
Serious infections	1.02 [0.72-1.44]	1.46 [0.83-2.59]	0.72 [0.50-1.03]
Venous thromboembolism	0.67 [0.35-1.29]	0.50 [0.09-2.67]	0.72 [0.20-1.30]
Major adverse cardiovascular events	0.37 [0.15-0.96]	--	1.54 [0.61-3.91]

Conclusion

Compared to TNF antagonists, JAK inhibitors were associated with a higher risk of overall infection, no signifcant difference for serioys infection and a lower risk of MACE.

References

1. The Lancet Gastroenterology H. New restrictions on JAK inhibitors in the EU. Lancet Gastroenterol Hepatol 2023;8:1.

2. Ananthakrishnan AN, Murad MH, Scott FI, et al. Comparative Efficacy of Advanced Therapies for Management of Moderate-to-Severe Ulcerative Colitis: 2024 American Gastroenterological Association Evidence Synthesis.

3. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med 2022;386:316-326.

4. Panes J, D'Haens GR, Sands BE, et al. Analysis of tofacitinib safety in ulcerative colitis from the completed global clinical developmental program up to 9.2 years of drug exposure. United European Gastroenterol J 2024;12:793-801.

Disclosure

DA: No relevant disclosures
KHY: No relevant disclosures
SBP: No relevant disclosures
SWG: No relevant disclosures
CM: Consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol
Myers Squibb, Celltrion, Eli Lilly, Ferring, Forte Biosciences, Fresenius Kabi,
Gilead, Janssen, McKesson, Mirador Therapeutics, Mylan, Pendopharm, Pfizer,
Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's
fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli
Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Organon, Pendopharm, Pfizer,
Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research
support from AbbVie, Eli Lilly, Ferring, Pfizer.
ANA: No relevant disclosures
NS: No relevant disclosures
VJ: Consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena
pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers
Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi,
Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan,
Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma,
Roche, Sandoz, Second Genome,Takeda, Teva, Topivert, Ventyx, Vividion;
speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda,
Fresenius Kabi
RX: No relevant disclosures
SS: Research grants from Pfizer

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

Optimising ulcerative colitis therapy (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

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

Wanshui Yang

SUGAR- AND LOW/NON-SUGAR-SWEETENED BEVERAGES AND RISKS OF METABOLIC DYSFUNCTION–ASSOCIATED STEATOTIC LIVER DISEASE AND LIVER-RELATED MORTALITY: A PROSPECTIVE ANALYSIS OF THE UK BIOBANK

Airong Wu

Panel discussion: Therapy update - EoE

Auto-brewery syndrome: A disease model

Gianluca Ianiro

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

Peter Irving

Biologic drugs

Luc Biedermann

UEG Presentation

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

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

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

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

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

Affiliations

1 Anhui Medical University, Hefei, China

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

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

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.

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

More Like This:

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

Wanshui Yang

SUGAR- AND LOW/NON-SUGAR-SWEETENED BEVERAGES AND RISKS OF METABOLIC DYSFUNCTION–ASSOCIATED STEATOTIC LIVER DISEASE AND LIVER-RELATED MORTALITY: A PROSPECTIVE ANALYSIS OF THE UK BIOBANK

Airong Wu

Panel discussion: Therapy update - EoE

Auto-brewery syndrome: A disease model

Gianluca Ianiro

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

Peter Irving

Biologic drugs

Luc Biedermann

UEG Presentation

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

SUGAR- AND LOW/NON-SUGAR-SWEETENED BEVERAGES AND RISKS OF METABOLIC DYSFUNCTION–ASSOCIATED STEATOTIC LIVER DISEASE AND LIVER-RELATED MORTALITY: A PROSPECTIVE ANALYSIS OF THE UK BIOBANK

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

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

SUGAR- AND LOW/NON-SUGAR-SWEETENED BEVERAGES AND RISKS OF METABOLIC DYSFUNCTION–ASSOCIATED STEATOTIC LIVER DISEASE AND LIVER-RELATED MORTALITY: A PROSPECTIVE ANALYSIS OF THE UK BIOBANK

Lihe Liu 1, Zhaoyang Zou 1, Guoting Xu 1, JINZHOU ZHU 2, RUI LI 3, Airong Wu 1

Affiliations

1 The First Affiliated Hospital of Soochow University, Suzhou, China

2 The first affiliated hospital of Soochow University, Suzhou, China

3 The First Affiliated Hospital Of Soochow University, Suzhou, China

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a critical component of multi-system metabolic dysfunction and has emerged as a significant global health issue. A growing body of evidence suggests that intake of sugar and its substitutes is linked to cardiometabolic and kidney diseases. While sugar-sweetened beverages (SSBs) and low- or non-sugar-sweetened beverages (LNSSBs) are widely consumed, their associations with liver health outcomes remain uncertain.

Aims & Methods

In this prospective cohort study of 103,251 UK Biobank participants free of baseline liver disease, we investigated the associations between SSBs and LNSSBs intake and the risk of incident MASLD and liver-related mortality. Beverage consumption was assessed through multiple 24-hour dietary questionnaires. The primary outcome was incident MASLD, and secondary outcomes included liver-related mortality and liver fat content measured by MRI- derived proton density fat fraction. Multivariable Cox regression, linear models, stratified analyses, restricted cubic spline, sensitivity analyses, and beverage substitution analyses were employed.

Results

Over a median 10.3-year follow-up, 949 participants developed MASLD, and 103 died from liver-related causes. Higher intake of LNSSBs (>330 g/day) and SSBs (>330 g/day) were associated with elevated MASLD risk (HR: 1.597 and 1.502, respectively; both p < 0.01). LNSSBs consumption also increased liver-related mortality risk in a dose-dependent manner, while no significant association was observed for SSBs. Both beverages were positively associated with liver fat content. Replacing 330 g/day of either beverage with water significantly reduced MASLD risk by 14.7% (SSBs) and 13.5% (LNSSBs), whereas substitution between LNSSBs and SSBs showed no difference in risk.

Conclusion

High intake of either SSBs or LNSSBs is significantly associated with an increased risk of MASLD, with LNSSBs additionally linked to a higher risk of liver-related mortality. Water substitution may offer benefits. These findings support limiting the intake of both SSBs and LNSSBs as part of comprehensive prevention strategies targeting cardio-renal-liver-metabolic dysfunction.

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

More Like This:

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

Wanshui Yang

SUGAR- AND LOW/NON-SUGAR-SWEETENED BEVERAGES AND RISKS OF METABOLIC DYSFUNCTION–ASSOCIATED STEATOTIC LIVER DISEASE AND LIVER-RELATED MORTALITY: A PROSPECTIVE ANALYSIS OF THE UK BIOBANK

Airong Wu

Panel discussion: Therapy update - EoE

Auto-brewery syndrome: A disease model

Gianluca Ianiro

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

Peter Irving

Biologic drugs

Luc Biedermann

UEG Presentation

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

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

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

Panel discussion: Therapy update - EoE

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

Event

UEG Week Berlin 2025

Topics

Mechanisms & Personalised Medicine Small Intestine & Nutrition Oesophagus Paediatrics

Session

Therapy update: EoE

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

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

Wanshui Yang

SUGAR- AND LOW/NON-SUGAR-SWEETENED BEVERAGES AND RISKS OF METABOLIC DYSFUNCTION–ASSOCIATED STEATOTIC LIVER DISEASE AND LIVER-RELATED MORTALITY: A PROSPECTIVE ANALYSIS OF THE UK BIOBANK

Airong Wu

Panel discussion: Therapy update - EoE

Auto-brewery syndrome: A disease model

Gianluca Ianiro

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

Peter Irving

Biologic drugs

Luc Biedermann

UEG Presentation

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

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

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

Auto-brewery syndrome: A disease model

Gianluca Ianiro 1

Affiliations

1 Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome, Rome, Italy

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

Event

UEG Week Berlin 2025

Topics

Mechanisms & Personalised Medicine

Session

Breath testing and clinical metabolomics: Back to the future

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

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

Wanshui Yang

SUGAR- AND LOW/NON-SUGAR-SWEETENED BEVERAGES AND RISKS OF METABOLIC DYSFUNCTION–ASSOCIATED STEATOTIC LIVER DISEASE AND LIVER-RELATED MORTALITY: A PROSPECTIVE ANALYSIS OF THE UK BIOBANK

Airong Wu

Panel discussion: Therapy update - EoE

Auto-brewery syndrome: A disease model

Gianluca Ianiro

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

Peter Irving

Biologic drugs

Luc Biedermann

UEG Presentation

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

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

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

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

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

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

Affiliations

1 Amsterdam University Medical Center, Amsterdam, Netherlands

2 Onze Lieven Vrouwen Gasthuis, Amsterdam, Netherlands

3 Vestre Viken HF, Gjettum, Norway

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

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

6 Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France

7 Akershus Universitetssykehus, Nordbyhagen, Norway

8 Baysient LLC, Fort Meyers, United States

9 BÜHLMANN Laboratories AG, Basel, Switzerland

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

11 Dova Health Intelligence, Vancouver, Canada

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

Introduction

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

Aims & Methods

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

Results

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

Table 1. Baseline characteristics

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

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

Conclusion

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

References

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

Disclosure

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

Event

UEG Week Berlin 2025

Topics

Endoscopy IBD Mechanisms & Personalised Medicine

Submission format

Late-Breaking Abstract

Session

Hot off the press: IBD treatment

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

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

Wanshui Yang

SUGAR- AND LOW/NON-SUGAR-SWEETENED BEVERAGES AND RISKS OF METABOLIC DYSFUNCTION–ASSOCIATED STEATOTIC LIVER DISEASE AND LIVER-RELATED MORTALITY: A PROSPECTIVE ANALYSIS OF THE UK BIOBANK

Airong Wu

Panel discussion: Therapy update - EoE

Auto-brewery syndrome: A disease model

Gianluca Ianiro

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

Peter Irving

Biologic drugs

Luc Biedermann

UEG Presentation

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

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

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

Biologic drugs

Luc Biedermann 1

Affiliations

1 USZ Zürich, Zürich, Switzerland

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

Event

UEG Week Berlin 2025

Topics

Mechanisms & Personalised Medicine Small Intestine & Nutrition Oesophagus Paediatrics

Session

Therapy update: EoE

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

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

Wanshui Yang

SUGAR- AND LOW/NON-SUGAR-SWEETENED BEVERAGES AND RISKS OF METABOLIC DYSFUNCTION–ASSOCIATED STEATOTIC LIVER DISEASE AND LIVER-RELATED MORTALITY: A PROSPECTIVE ANALYSIS OF THE UK BIOBANK

Airong Wu

Panel discussion: Therapy update - EoE

Auto-brewery syndrome: A disease model

Gianluca Ianiro

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

Peter Irving

Biologic drugs

Luc Biedermann

UEG's educational platform for gastroenterology education bringing recordings, courses, guidelines, and more together in one place.

Most popular content

Rate for better recommendations!