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

Free for all myUEG account holders. Your access level is set automatically based on your occupation. Medical professionals get full access to all content. If you are a non-medical user, you can only access UEG Week content from congresses you attended.

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

Introduction

Severe Crohn's disease (CD) may progress to short bowel syndrome (SBS). Teduglutide stands as a validated treatment for SBS offering promising results for these patients.

Aims & Methods

This study aims to evaluate the performance of teduglutide in the subgroup of patients with SBS secondary to CD. We performed a systematic review in PubMed, Embase and Cochrane databases, searching for studies with patients with SBS and CD treated with teduglutide. The primary outcome was the reduction of parenteral support (PS). The secondary outcome was discontinuation of PS. The odds ratio (OR) was used for binary outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I² statistics.

Results

The meta-analyses included 4 studies and 77 patients. All studies evaluated PS reduction and teduglutide demonstrated a good performance (PS reduction in 79.94% of the patients; 95% CI 57.97% to 100.00%; I2=85%). Three studies (61 patients) evaluated PS discontinuation and teduglutide demonstrated a good performance too (PS discontinuation in 28.59% of the patients; 95% CI 17.43% to 39.75%; I2=0%).

Conclusion

Teduglutide is a good therapeutic option for patients with SBS in the subgroup of CD patients, improving PS reduction and discontinuation and leading to better quality of life of these patients.

References

1. Joly F, Seguy D, Nuzzo A, Chambrier C, Beau P, Poullenot F, et al. Six-month outcomes of teduglutide treatment in adult patients with short bowel syndrome with chronic intestinal failure: A real-world French observational cohort study. Clin Nutr Edinb Scotl. 2020 Sep;39(9):2856–62.
2. Kochar B, Long MD, Shelton E, Young L, Farraye FA, Yajnik V, et al. Safety and Efficacy of Teduglutide (Gattex) in Patients With Crohn’s Disease and Need for Parenteral Support Due to Short Bowel Syndrome-associated Intestinal Failure. J Clin Gastroenterol. 2017 Jul;51(6):508–11.
3. Sato T, Uchino M, Takeuchi J, Fujihira Y, Shimizu K, Yokoyama K, et al. Short-term clinical evaluation of teduglutide for patients with Crohn’s disease on home parenteral support for postoperative short bowel syndrome with intestinal failure. Clin Nutr Edinb Scotl. 2023 May;42(5):722–31.
4. Siu RK, Karime C, Hashash JG, Kinnucan J, Picco MF, Farraye FA. Improved Outcomes Associated With Teduglutide Use in Patients With Both Short Bowel Syndrome and Crohn’s Disease. Crohns Colitis 360. 2024 Jan;6(1):otae007.

TEDUGLUTIDE FOR THE TREATMENT OF SHORT BOWEL SYNDROME IN CROHN'S DISEASE PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Natália Junkes Milioli 1, Vanio Antunes 2, Tulio Loyola Correa 3, Otávio Martins 4, Alonzo Prata 5, Ana carolina Covre Coan 5, Andre Milani 6, Elisio Bulhões 7, Pedro Romeiro 8, Matheus Fernandes 2

1 Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil

2 Federal University of Health Science of Porto Alegre, Porto Alegre, Brazil

3 Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, United States

4 Federal University of Juiz de Fora, Juiz de Fora, Brazil

5 Federal University of Espirito Santo, Vitória, Brazil

6 State University of Campinas, Campinas, Brazil

7 College of Higher Education of the United Amazon, Redenção, Brazil

8 Department of Medicine, University Center of Maceió, Maceió, Brazil

Conference

UEG Week Vienna 2024

Topics

IBD

Submission format

Abstract

Session

IBD (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Presentation

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

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

Understanding the role of diet in the pathogenesis of lower GI disease

Timon Adolph 1

1 Univ.-Klinik für Innere Medizin / Univ.-Klinik für Innere Medizin I, Innsbruck, Austria

Event

UEG Week Vienna 2024

Topics

IBD Small Intestine & Nutrition Primary Care

Session

Nutrition in pathogenesis and treatment of lower GI disorders

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Presentation

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

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

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

Introduction

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

Aims & Methods

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

Results

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

Conclusion

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

Disclosure

No disclosures

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

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

1 Gastroenterology Aalesund, Alesund, Norway

2 Central Hosspital of Ostfold, Grålum, Norway

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

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

Event

UEG Week Berlin 2025

Topics

Endoscopy IBD

Submission format

Abstract

Session

Tackling IBD in clinics

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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

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

Artificial intelligence: View of the pathologist and endoscopist

Marietta Iacucci 1, Rupert Langer 2

1 University of Birmingham, Birmingham, United Kingdom

2 TU Muniche, Muniche, Germany

Event

UEG Week Vienna 2024

Topics

Endoscopy Histopathology IBD Radiology & Imaging

Session

What's new in AI in lower GI in 2024?

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Presentation

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

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

Initial management of Crohn's disease: Time for a new paradigm?

Nurulamin Noor 1

1 Cambridge University Hospitals, Cambridge, United Kingdom

Event

UEG Week Vienna 2024

Topics

IBD Immunology Surgery

Session

IBD: Maximising therapy success

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Presentation

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

BIOLOGIC DRUG AND ANTI-DRUG ANTIBODY MONITORING: TNF INHIBITORS, INFLIXIMAB, ADALIMUMAB, AND CERTOLIZUMAB PEGOL, IN 128,537 PATIENT SAMPLES

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

Introduction

Serum assays to measure biologic drugs, especially TNF inhibitors, and their anti-drug antibodies (ADAb) are utilized to manage suboptimal response and to proactively titrate doses and dosing intervals. Sensitive, drug-tolerant and high-resolution anti-drug antibody assays are an increasingly important tool necessary for detection and management of immunogenicity, especially when low-intermediate in titer and potentially reversible.¹

Aims & Methods

Serum samples from 72,819, 53,131, and 2587 patients were analyzed for infliximab (IFX), adalimumab (ADL), and certolizumab pegol (CTZ) drug (in μg/mL) and corresponding anti-drug antibodies (in ng/mL) as measured by drug-specific lab developed chemiluminescent immunoassays. Drug assays measure the free ADAb-unbound fraction of drug when serum ADAb are present. All ADAb assays detect total antibodies (including IgM & IgG subtypes), and their drug tolerance has been validated. Drug-specificity of ADAbs is verified by a confirmatory test step. An extensive blinded method comparison of our IFX and Anti-IFX assays has been published.²

Results

Drug and ADAb results are summarized in Table 1. Immungenicity rates were 31%, 29%, and 68% for IFX, ADL, and CTZ, respectively. ADAb-free samples were used to evaluate distribution of drug levels. Even in the absence of immunogenicity, many patients are subtherapeutic, 25%, 45% and 40%, for IFX, ADL, and CTZ, respectively, when using proposed therapeutic targets of 5 μg/mL for IFX, 7.5 for ADL, and 20 for CTZ.³ Therapeutic levels were observed in 27% for IFX, 37% for ADL and 32% for CTZ. Higher drug concentrations in the remaining samples may represent non-trough collected samples.

A wide range of immunogenicity titers was observed. Analyses of the inverse relationship between ADAb and drug led to determination of cut-points for low/high titer designations where in the setting of high ADAb, almost invariably, concomitant free drug is very low or nil. As a good rule, anti-drug antibodies should be interpreted in the context of the concomitant free drug trough concentration.

Table 1. Analysis of Patient Samples for IFX, ADL, CTZ and Respective Anti-Drug Antibodies

	IFX	ADL	CTZ
Therapeutic Target Drug Concentration (ug/mL)³	5.0	7.5	20.0
Range of Drug Concentrations in ADAb-Negative Samples	n=50,325 0.4 to 593 μg/mL	n=37,653 0.6 to 74 μg/mL	n=837 1.0 to 138 μg/mL
Distribution of Drug Concentrations in Anti-Drug Ab-negative samples	25%: <5.0 μg/mL 27%: 5-10 μg/mL 27%: 11-20 μg/mL 21%: >20 μg/mL	45%: <7.5 μg/mL 37%:7.5-12 μg/mL 14%: 13-20 μg/mL 4%: >20 μg/mL	40%: <20 μg/mL 32%: 20-39 μg/mL 28%: >40 μg/mL
Immunogenicity	n=22,494 31%	n-15,478 29%	n=1750 68%
Range of ADAb Titers	22 to 582,749 ng/mL	25 to 863,115 ng/mL	40 to 236,148 ng/mL
Anti-Drug Ab Titer Designation Cut-points (ng/mL)	Low: <200 High: >1000	Low: <100 High: >800	Low: <1000 High: >5000
Inverse Relationship Between Drug and Anti-Drug Ab Levels?	yes	yes	yes
Interpretive Comments for Anti-Drug Ab	Anti-drug antibody levels should be interpreted in the context of the concomitant free drug concentration at trough.Low titer anti-drug antibodies may be transient while high titers are likely to be more consequential.
Interpretive Comments for Anti-Drug Ab	Some immunogenicity is reversible. Elimination of intermediate titer and some high titer anti-drug antibodies has been achieved with dose escalation and/or methotrexate or thiopurine.		Non-neutralizing anti-pegol antibodies cannot be ruled out.

Conclusion

Here, we report concentrations of TNF-inhibitors used to treat IBD and their anti-drug antibodies in >128,000 patient samples. Though clinical histories and blood collection timing are not known, we observed that many patients may have insufficient drug levels. Immunogenicity to TNF inhibitors was frequent where a wide numeric range of ADAb was observed. Numeric ADAb antibody results should be interpreted with the help of titer designations by the laboratory because low to intermediate titers may be transient or reversible whereas high titers with nil or very low drug indicate refractory immunogenicity. High resolution ADAb assays have enabled the early detection and successful reversal of intermediate titers of Anti-IFX and Anti-ADL with dose escalation +/- co-immunommodulator.¹ Thus, biologic TDM aims to optimize drug efficacy and longevity by informing and expediting adjustments to medication.

References

1. Colman RJ et al. Antibodies-to-infliximab accelerate clearance while dose intensification reverses immunogenicity and recaptures clinical response in paediatric Crohn’s disease. Aliment Pharmacol Ther. 2022;55:593–603.

2. Marini J et al. Comparisons of Serum Infliximab and Antibodies-to-Infliximab Tests Used in Inflammatory Bowel Disease Clinical Trials of Remicade. American Association of Pharmaceutical Scientists Journal 2016 DOI: 10.1208/s12248-016-9981-3.

3. Feuerstein JD et al. American Gastroenterological Association Institute Guideline on Therapeutic Drug Monitoring in Inflammatory Bowel Disease. Gastroenterology 2017;153:827–834.

BIOLOGIC DRUG AND ANTI-DRUG ANTIBODY MONITORING: TNF INHIBITORS, INFLIXIMAB, ADALIMUMAB, AND CERTOLIZUMAB PEGOL, IN 128,537 PATIENT SAMPLES

Kelly Y. Chun 1, Jane Yang 1

1 Labcorp, Calabasas, United States

Event

UEG Week Vienna 2024

Topics

IBD Mechanisms & Personalised Medicine Radiology & Imaging

Submission format

Abstract

Session

IBD: Diagnosis and monitoring

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Poster

Standard Poster

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

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

Introduction

There is a need for more effective treatments for IBD, with advanced therapies having placebo-adjusted clinical remission rates of only 10 to 25%. The combined use of targeted biologic agents could break through this efficacy ceiling while avoiding the risks associated with broad immunosuppression. Towards this end, Spyre Therapeutics is developing half-life extended antibody drug candidates that can be administered in combination, inhibiting the clinically validated IBD targets α4β7 integrin (SPY001), TL1A (SPY002), and IL-23 (SPY003). The efficacy of combined inhibition of integrin β7 and TL1A, integrin β7 and IL-23, and TL1A and IL-23 was evaluated in proof-of-concept studies utilizing the TNBS-induced murine colitis model.

Aims & Methods

Mice were dosed intravenously with surrogate antibodies targeting mouse integrin β7 (25 mg/kg), mouse TL1A (25 mg/kg), mouse IL-23 (25 or 1 mg/kg), pairwise combinations of these three antibodies (integrin β7 + TL1A, integrin β7 + IL-23, TL1A + IL-23), an isotype control antibody, or vehicle on Day -1 and Day 2. TNBS was administered intrarectally (IR) on day 0 to induce colitis in all mice except the non-disease control group, which received IR vehicle. Body weight and disease activity score were recorded daily until the end of the study on Day 6. Colon weight and length were measured at the conclusion of the study. Colon histopathology was scored by a blinded pathologist.

Results

Monotherapy treatment with 25 mg/kg anti-β7 or 25 mg/kg anti-TL1A antibodies resulted in low magnitude, directional improvements in colitis outcome measurements, while treatment with 25 mg/kg anti-IL-23 antibody resulted in significant improvements relative to the vehicle and isotype control groups. Combinations of anti-β7 + anti-TL1A, anti-β7 + anti-IL-23, and anti-TL1A + anti-IL-23 resulted in superior efficacy compared to their constituent monotherapies based upon disease activity scoring. To further explore combination therapy benefit, a lower dose (1 mg/kg) of anti-IL-23 alone or in combination with anti-β7 or anti-TL1A was evaluated. Low dose anti-IL-23 showed minimal activity as a monotherapy, but low dose anti-IL-23 + anti-β7 maintained efficacy similar to the high dose combination. The combination of low dose anti-IL-23 + anti-TL1A was more effective than either monotherapy alone.

Conclusion

Combination therapy with anti-β7 + anti-TL1A, anti-β7 + anti-IL-23 or anti-TL1A + anti-IL-23 resulted in efficacy superior to their constituent monotherapies in the murine TNBS model of colitis. These data support and provide biologic rationale for the advancement of antibody combinations into human clinical trials for inflammatory bowel disease.