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Introduction

Long-term antithrombotic therapy is recommended in short bowel syndrome (SBS) caused by acute mesenteric ischemia (AMI). However, evidence-based recommendations on drug choice, duration and monitoring of treatment are lacking. Also, guidelines are based on data on other artery diseases and overlook the altered drug absorption in patients with SBS. To understand current practices, we aimed to assess the long-term antithrombotic management of AMI.

Aims & Methods

An online survey was sent to centers contributing to the chronic intestinal failure database of the HAN-CIF (Home Artificial Nutrition – Chronic Intestinal Failure) special interest group of ESPEN (European Society on Clinical nutrition and Metabolism), treating patients with SBS post-AMI. The survey featured 10 cases varying in postsurgical intestinal anatomy, revascularization and etiology and focused on drug class, administration route, duration and monitoring of antithrombotic therapy.

Results

The survey was completed by 43 centers. In case of idiopathic AMI leading to SBS, anticoagulation (65.1% of all physicians) or antiplatelet (32.6%) therapy were mostly prescribed (Figure 1; jejunocolic anastomosis, idiopathic). Antiplatelet therapy was prescribed more often to patients with type 3 anatomy (37.2%, largest absorptive capacity) than to other anatomy groups (30.2 and 32.6% in type 1 and 2 respectively). Antiplatelet drugs (39.5%) or combination therapy (18.6%) were more commonly prescribed in case of revascularization compared to no revascularization (32.6% or 2.3% respectively). Anticoagulants were very common in patients with atrial fibrillation (90.7%), venous thrombosis (95.3%) and antiphospholipid syndrome (83.7%). More antiplatelet drugs (27.9%) or combination therapy (18.6%) were preferred with concomitant peripheral artery disease. In hypovolemic shock, no therapy (41.9%) or anticoagulants (51.2%) were common.
Parenteral drugs were more prescribed to patients with type 1 anatomy (51.2% of all physicians; lowest absorptive capacity) than to patients with type 2 (44.2%) or 3 (20.9%) anatomy.
Antiplatelet drugs were mainly prescribed lifelong (94.7% of this drug class), while anticoagulants were prescribed for 6 (19.4%) to 12 (16.1%) months or lifelong (51.6%), irrespective of anatomy, revascularization or etiology.
Vitamin K antagonists were consistently monitored, whereas aspirin was not. Monitoring of subcutaneous low molecular weight heparins (no monitoring, 36.8% - always monitoring, 42.1% - in specific circumstances, 21.0%) and non-vitamin K oral anticoagulants varied (no monitoring, 50.0%).

Conclusion

In a case-based survey, anticoagulant versus antiplatelet drug choice depended on the anatomy, revascularization and etiology. However, there was a high variability in case of idiopathic AMI. Administration route depended on anatomy. More detailed practice guidelines are needed.

Disclosure

TV has participated in advisory boards, as a consultant and/or as a speaker on behalf of Boehringer Ingelheim, Bayer, Daiichi Sankyo, BMS/Pfizer, Sanofi Aventis, and Leo Pharma

EXAMINING LONG-TERM ANTITHROMBOTIC TREATMENT PATTERNS IN PATIENTS WITH SHORT BOWEL SYNDROME POST ACUTE MESENTERIC ISCHEMIA: INSIGHTS FROM AN INTERNATIONAL SURVEY

Barbara Deleenheer 1, Cristina Cuerda 2, Palle Bekker Jeppesen 3, Francisca Joly 4, Simon Lal 5, Georg Lamprecht 6, Mundi Manpreet 7, Loris Pironi 8, Kinga Szczepanek 9, Thomas Vanassche 10, Lorenz Van der Linden 11, André Van Gossum 12, Geert J.A. Wanten 13, Tim Vanuytsel 11

1 KU Leuven, Leuven, Belgium|||University Hospitals Leuven, Leuven, Belgium|||University Hospitals Leuven, Leuven, Belgium

2 Hospital General Universitario Gregorio Marañón, Madrid, Spain

3 Rigshospitalet, Copenhagen, Denmark

4 Beaujon Hospital Service de Gastroenterologie, Clichy, France

5 Salford Royal Foundation Trust, Salford, United Kingdom

6 Rostock University Medical Center, Rostock, Germany

7 Mayo Clinic, Rochester, United States

8 University of Bologna S. Orsola-Malpighi Hospital, Bologna, Italy

9 Stanley Dudrick’s Memorial Hospital, Skawina, Poland

10 University Hospitals Leuven, Leuven, Belgium

11 KU Leuven, Leuven, Belgium|||University Hospitals Leuven, Leuven, Belgium

12 Hôpital Erasme, University of Brussels, Bruxelles, Belgium

13 Radboud University Nijmegen, Nijmegen, Netherlands

Conference

UEG Week Vienna 2024

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

SMALL INTESTINAL (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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EARLY RESPONSE TO GLEPAGLUTIDE, A NOVEL LONG-ACTING GLP-2 ANALOG, IN SHORT BOWEL SYNDROME PATIENTS WITH INTESTINAL FAILURE: RESULTS OF 24-WEEK PHASE 3 TRIAL

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Introduction

Management of short bowel syndrome (SBS) patients with intestinal failure (IF) is multidisciplinary and multifactorial. The goal of treatment is to enhance oral/enteral nutrition as early as possible in a safe and well-tolerated manner. This can be achieved by increasing intestinal absorptive capacity to reduce parenteral support (PS) and in some patients avoid the need for central lines after achieving enteral autonomy. Glepaglutide is a novel long-acting GLP-2 analog in an aqueous formulation developed for subcutaneous (SC) weekly administration.

Aims & Methods

The aim of EASE (Efficacy and Safety Evaluation) SBS-1 trial was to assess the efficacy and safety of glepaglutide in reducing PS in SBS patients with IF. The design was a 29-center, placebo-controlled, randomized, parallel-group, double-blind, 24-week phase 3 trial. Adult SBS patients with chronic IF and requiring PS at least 3 days per week were eligible. Patients were randomized to SC injections of either 10 mg glepaglutide twice-weekly (TW), 10 mg glepaglutide once-weekly (OW), or placebo. PS volume requirements were adjusted using a predefined algorithm. Primary endpoint was change in PS volume from baseline to week 24 and two of key secondary endpoints were change in PS volume from baseline to week 12 and achieving enteral autonomy (complete weaning-off PS) at week 24.

Results

106 optimized stable patients were randomized and 96% completed the trial. Treatment arms were well balanced and as expected for demographics: mean age of 55 years and 57% were women. Similarly balanced for baseline characteristics: 51% with colon-in-continuity (CiC), mean PS volume requirement of 14.4 L/week; 33% and 58% of patients with mild to moderate hepatic and renal impairment, respectively. Glepaglutide TW treatment significantly reduced PS vs placebo (mean change of -5.13 vs -2.85 L/week; estimated difference of -2.28 L/week; p=0.0039) at 24 weeks. Significant reduction in PS with glepaglutide TW was observed by week 12 with mean change of -4.32 vs -1.90 L/week; estimated difference of -2.42 L/week; p=0.0019). These findings were preserved in both anatomical subgroups: patients without and with CiC. No statistically significant reduction in PS was observed with glepaglutide OW vs placebo at week 12 or 24. Enteral autonomy was achieved for 5 (14%) patients receiving glepaglutide TW and 4 (11%) patients receiving glepaglutide OW vs 0 patients receiving placebo. In a post-hoc analysis, circulating levels of citrulline, a marker for intestinal mucosal cell mass, increased and were sustained from baseline to week 4 and 24 with a ratio of 1.49 (p<0.0001) and 1.41 (p=0.0101) in glepaglutide TW treatment arm vs placebo, respectively. Treatment with glepaglutide was assessed to be safe with more adverse events reported in glepaglutide treatment arms vs placebo, primarily attributable to mild injection site reactions.

Conclusion

Treating SBS patients with chronic IF with glepaglutide was assessed to be safe, well tolerated and resulted in early (by 12 weeks of treatment) sustained reductions in PS needs including the achievement of enteral autonomy in a meaningful number of patients within 24 weeks. Data supports glepaglutide as a novel medical treatment option for the management of SBS patients that results in early and significant reductions in PS support.

Disclosure

Nothing to disclose

EARLY RESPONSE TO GLEPAGLUTIDE, A NOVEL LONG-ACTING GLP-2 ANALOG, IN SHORT BOWEL SYNDROME PATIENTS WITH INTESTINAL FAILURE: RESULTS OF 24-WEEK PHASE 3 TRIAL

Tim Vanuytsel 1, Ulrich-Frank Pape 2, Sukanya Subramanian 3, Francisca Joly 4, Geert J.A. Wanten 5, Georg Lamprecht 6, Marek Kunecki 7, Faqooq Rahman 8, Thor Schutt Svane Nielsen 9, Lykke Bjerglund Graff 9, Mark Berner-Hansen 9, David F Mercer 10, Palle Bekker Jeppesen 11

1 University Hospital, Leuven, Belgium

2 Asklepios Medical School, Berlin, Germany

3 MedStar Georgetown, Washington DC, United States

4 Hospital Beaujon, Clichy, France

5 Radboud University Nijmegen Medical Centre (Radboud UMCN), Nijmegen, Netherlands

6 University Medical Center Rostock, Rostock, Germany

7 M. Pirogow Hospital, Wolczanska, Poland

8 University College London Hospitals (UCLH), London, United Kingdom

9 Zealand Pharma A/S, Copenhagen, Denmark

10 Nebraska Medical Center, Nebraska, United States

11 Rigshospitalet, Copenhagen, Denmark

Event

UEG Week Copenhagen 2023

Topics

Hepatobiliary IBD Small Intestine & Nutrition

Submission format

Abstract

Session

Big steps for coeliac and short bowel

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Introduction

Short bowel syndrome (SBS) is the most common cause of intestinal failure (IF) in children and is generally managed using parenteral nutrition and/or intravenous fluids (PN/IV). Long-term PN/IV can cause potentially life-threatening complications. Patients may receive teduglutide (TED) to encourage adaptation of the remaining intestine and to reduce dependence on PN/IV. Short-term studies have shown that TED is effective and has an acceptable safety profile in children and adults with SBS-associated IF (SBS-IF). However, assessment of long-term treatment with TED in paediatric patients with SBS-IF is limited.

Aims & Methods

We report real-world long-term safety and effectiveness data of TED from a paediatric cohort enrolled in the prospective, multinational SBS Registry (NCT01990040; EUPAS7973). Data were analysed cumulatively for up to 6 years between enrolment and interim data cut-off (June 23, 2014 to June 30, 2023). Patients were categorised based on whether they received TED (ever-treated; received ≥1 dose of TED 0.05 mg/kg/day [median]) or never received TED (never-treated; received PN/IV for ≥6 months before study entry). Safety endpoints included: occurrence of colorectal cancer in patients with any remnant colon; other malignancy; colorectal polyps; and adverse events (AEs). Effectiveness endpoints included clinical response (≥20% reduction in PN/IV volume from baseline) and change from baseline in volume of PN/IV (per weight [L/kg]) and number of days/week receiving PN/IV.

Results

In total, 398 paediatric patients were enrolled: 266 never-treated, 132 ever-treated (per-protocol set, n=397; 266 never-treated, 131 ever-treated). Patients had a mean (standard deviation [SD]) age of 5.4 (4.01) years (ever-treated 6.8 [4.12] years; never-treated 4.8 [3.80] years) and the majority were male (63.7%; ever-treated 68.7%; never-treated 61.3%). The median (range) length of exposure in ever-treated patients was 29.0 (1.15–106.61) months.
No new cases of colorectal cancer or new/worsening colorectal polyps were reported between baseline and interim cut-off. New/worsening malignancies were reported for one never-treated patient. A greater proportion of ever-treated patients reported AEs (87.0% vs 74.4%) and serious AEs (SAEs; 72.5% vs 59.0%) than never-treated patients. AEs and SAEs related to TED were reported in 15.3% and 6.1% of ever-treated patients, respectively. There were no allergic or hypersensitivity reactions to TED. The most common TED-related AEs were vomiting (3.8%) and abdominal pain (2.3%). Fatal events were recorded for one ever-treated and three never-treated patients.
A greater proportion of ever-treated patients had achieved a clinical response (year 1, 18/30, 60.0%; year 3, 11/17, 64.7%) than never-treated patients (year 1, 23/100, 23.0%; year 3, 17/82, 20.7%). Ever-treated patients had a greater mean (SD) reduction from baseline in PN/IV volume (L/kg; ever-treated: year 1, −39.4% [35.97], n=19; year 3, −61.6% [23.64]; n=7; never-treated: year 1, −21.1% [50.70], n=80; year 3, −34.4% [36.83], n=49) and number of days/week receiving PN/IV (ever-treated: year 1, −1.6 [2.16], n=30; year 3, −1.5 [1.77], n=17; never-treated: year 1, −1.0 [2.22], n=100; year 3, −0.6 [1.51]; n=82) than never-treated patients.

Conclusion

This 6-year interim analysis of real-world data from a large cohort of paediatric patients with SBS-IF supports that the safety profile of TED is consistent with the previous 5-year follow-up and suggests that TED improves intestinal adaptation in paediatric patients with SBS-IF over a 3-year period.

Disclosure

Palle B Jeppesen: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; commercial relationships as consultant and speaker with Albumedix, ArTara Therapeutics, Baxter, Coloplast, Ferring Pharmaceuticals, Fresenius Kabi, GLyPharma Therapeutic, Ironwood Pharmaceuticals, Naia Pharmaceuticals, NorthSea Therapeutics, Novo Nordisk Foundation, Protara Therapeutics, Takeda, Therachon, VectivBio and Zealand Pharma.
Martina Kohl-Sobania: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; study investigator for NPS Pharmaceuticals and Takeda; honoraria from Aposan, Takeda and Tauro-Implant as a speaker; advisory board member for Takeda.
Francisca Joly: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; study investigator for NPS Pharmaceuticals, Takeda, VectivBio and Zealand Pharma; advisory board member for Alira Health, ArTara Therapeutics, Baxter, M3E Solutions, Takeda, Therachon, VectivBio and Zealand Pharma; commercial relationships as consultant and speaker for Baxter, B. Braun, Fresenius Kabi, Nestlé Health Sciences, Takeda, Therachon and Théradial.
Joel B Mason: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; research support from Takeda as a site for the study; compensation from Care/of, a producer of nutritional supplements; honoraria from UpToDate, a web-based medical information platform, for authoring chapters.
Johane P Allard: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; fees from Takeda as a consultant and speaker, and research support from Takeda as a study site principal investigator (PI); research support from Fresenius Kabi and OMS as a PI; honoraria from Baxter as a speaker and consultant; research support from Zealand Pharma as a site PI.
Ulrich-Frank Pape: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; honoraria from Takeda as a consultant and speaker, and research support from Takeda, VectivBio and Zealand Pharma as a study site PI.
Loris Pironi: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; advisory board member for Baxter, NorthSea Therapeutics and Takeda.
Gabriel E Gondolesi: speaker for Takeda; compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; received investigator-initiated research grant from Takeda.
Lauren K Schwartz: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; speaker for Bristol Myers Squibb; advisory board member for Takeda.
Pinggao Zhang, Sasan Sabrdaran and Yi Wen Huang: employees of Takeda Pharmaceuticals U.S.A., Inc. and receive stock and/or stock options.
André Gabriel: former employee of Takeda Pharmaceuticals U.S.A., Inc. who received stock and/or stock options.

Acknowledgements: This study was funded by Takeda Pharmaceuticals U.S.A., Inc., MA, USA. Medical writing support, funded by Takeda Pharmaceuticals U.S.A., Inc., was provided by Elizabeth Coe, PhD of PharmaGenesis Cardiff, Cardiff, UK.

LONG-TERM SAFETY AND EFFECTIVENESS OF TEDUGLUTIDE IN PAEDIATRIC PATIENTS WITH SHORT BOWEL SYNDROME-ASSOCIATED INTESTINAL FAILURE: AN OBSERVATIONAL, PROSPECTIVE, MULTICENTRE REGISTRY

Palle Bekker Jeppesen 1, Martina Kohl-Sobania 2, Francisca Joly 3, Joel B Mason 4, Johane Allard 5, Ulrich-Frank Pape 6, Loris Pironi 7, Gabriel E Gondolesi 8, Lauren K Schwartz 9, Pinggao Zhang 10, André Gabriel 10, Sasan Sabrdaran 10, Yi Wen Huang 10

1 Rigshospitalet, Copenhagen, Denmark

2 University Hospital Schleswig-Holstein, Lübeck, Germany

3 Hôpital Beaujon, Clichy, France

4 Tufts Medical Center, Boston, United States

5 Toronto General Hospital, Toronto, Canada

6 Asklepios Medical School, Hamburg, Germany

7 St. Orsola Hospital, University of Bologna, Bologna, Italy

8 Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina

9 NYU Langone Medical Center, New York, United States

10 Takeda Development Center Americas, Inc., Cambridge, United States

Conference

UEG Week Vienna 2024

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

Short bowel and nutrition therapies (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Introduction

SBS-IF is a severe organ failure with long-term parenteral support (PS) dependence. GLP-2 stimulates intestinal adaptation resulting in increased absorptive capacity. Apraglutide (APRA) is a novel long-acting GLP-2 analog in development for SBS-IF. This multicenter, open-label, phase 2 study in SBS-IF-CiC aims to investigate the safety and clinical efficacy of APRA at 52 weeks (W).

Aims & Methods

STARS Nutrition is a 52W open-label study in 9 adult SBS-IF–CiC pts receiving once-weekly subcutaneous APRA injections (5 mg). Metabolic balance studies were performed at baseline and 4W with stable PS, followed by a 48-W PS adjustment period. During monthly 48-hour fluid balance assessments, oral fluid intake was kept constant by adhering to an individual predefined drinking menu while measuring urine volume. PS was reduced according to an algorithm if an increase in mean daily urinary output of ≥10% was observed. As part of patient-reported outcomes (PRO), Patient Global Impression of Change (PGIC) v2.0 (5-point verbal response scale from 2= much better to -2= much worse) was used to assess overall change in pts’ status since APRA use. Safety was the primary endpoint. Secondary endpoints included changes in weekly PS volume, energy content, and PS days, proportion of clinical responders (≥20% PS reduction) and changes in PGIC at 52W. Data are presented as mean (95% CI) unless otherwise specified. Nominal p-values are calculated using paired T-tests with significance set at 0.05.

Results

APRA had an acceptable safety profile. All pts experienced ≥1 adverse event (AE); a total of 127 AEs were reported. Three pts experienced serious AEs. APRA was interrupted for 1 week in one pt with acute cholangitis and restarted successfully to trial completion. Absolute weekly PS volume decreased significantly by -4702 (-6539 to -2865) mL/week representing a 52% reduction from baseline (p=0.0004). Accordingly, PS energy content significantly decreased by -3510 (-4991 to -2029) kcal/week (p=0.0006). All pts qualified as clinical responders. Seven pts (78%) achieved ≥1 day off PS of whom two pts (22%) reached enteral autonomy. Pts gained an additional 2.1 (0.7–3.6) days off per week. Total body and lean body weight; and daily urine output remained stable despite PS reductions. All pts experienced a subjective improvement of their general condition based on the PGIC: eight pts reported a score of 2 (much better) and one pt reported a score of 1 (little better).

Conclusion

STARS Nutrition prospectively shows evidence for clinical benefit of a long-acting GLP-2 analog in SBS-IF–CiC. APRA has an acceptable safety profile and is associated with significant reductions in PS needs in pts with SBS-IF–CiC resulting in days without PS and subjective improvement based on PRO.

Disclosure

Astrid Verbiest, Mark Krogh Hvistendahl – nothing to declare.
Palle Bekker Jeppesen – received grants/research support/honoraria or consultation fees from Agomab, Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast, Ferring, Fresenius Kabi, GLyPharma, Naia Pharma, NPS Pharmaceuticals, NorthSea Therapeutics, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectivBio and Zealand Pharma.
Francisca Joly – has received grants/research support/honoraria or consultation fees from Agomab, Baxter, Fresenius Kabi, Nestlé Health Sciences, BBraun, Theradial, Mayoli, Biocodex, mobile3e Consulting, Carembouche, NPS Pharmaceuticals, NorthSea Therapeutics, Shire, Takeda, Therachon, VectivBio and Zealand Pharma.
Tim Vanuytsel – has served on the speaker bureau for Abbott, Agomab, Baxter, Biocodex, Dr. Falk Pharma, Fresenius Kabi, Ipsen, Menarini, Microbiotica, MyHealth, Remedus, Takeda, Truvion, VectivBio and Zealand Pharma. TV has provided clinical advice to Baxter, Danone, Dr. Falk Pharma, MyHealth, NorthSea Therapeutics, Shire, Therachon, Takeda, VectivBio, Zealand Pharma. TV has received research grants from Danone, MyHealth, Takeda and VectivBio.
Federico Bolognani, Carrie Li and Nader N. Youssef – employees of VectivBio/Ironwood.
This research was supported by VectivBio AG/Ironwood.

ONE-YEAR TREATMENT WITH THE LONG-ACTING GLUCAGON-LIKE PEPTIDE-2 (GLP-2) ANALOG APRAGLUTIDE RESULTS IN PARENTERAL SUPPORT WEANING, CLINICAL BENEFIT AND IMPROVED PATIENT REPORTED OUTCOMES IN SHORT BOWEL SYNDROME WITH INTESTINAL FAILURE (SBS-IF) AND COLON-IN

Astrid Verbiest 1, Mark Krogh Hvistendahl 2, Federico Bolognani 3, Carrie Li 3, Nader N. Youssef 3, Palle Bekker Jeppesen 2, Francisca Joly 4, Tim Vanuytsel 1

1 University of Leuven, Leuven, Belgium|||University Hospitals Leuven, Leuven, Belgium

2 Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

3 VectivBio/Ironwood, Basel, Switzerland

4 Hôpital Beaujon, Clichy, France

Conference

UEG Week Vienna 2024

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

Short bowel and nutrition therapies (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Presentation

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MAGNETIC RESONANCE IMAGING (MRI) SHOWS CHANGES IN BOWEL MORPHOLOGY AND MOTILITY IN SHORT BOWEL SYNDROME WITH INTESTINAL FAILURE (SBS-IF) AND COLON-IN-CONTINUITY (CIC) AFTER TREATMENT WITH THE LONG-ACTING GLUCAGON-LIKE PEPTIDE-2 (GLP-2) ANALOG APRAGLUTIDE

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Introduction

SBS-IF is a severe organ failure with long-term parenteral support (PS) dependence. In the first years after extensive surgery, spontaneous structural (elongation of intestinal villi and crypts) and functional (incl. motility) intestinal changes occur, stimulating a more efficient nutrient and fluid absorption in the remnant bowel. GLP-2 analogs are hypothesized to boost intestinal adaptation resulting in increased intestinal absorption and reduced PS needs. Apraglutide (APRA) is a long-acting GLP-2 analog in development for SBS-IF. We investigated the effect of APRA at 52 weeks (W) on bowel morphology and motility based on magnetic resonance imaging (MRI).

Aims & Methods

STARS Nutrition is a 52-W multicenter, open-label, phase 2 study in adult SBS-IF-CiC pts receiving weekly subcutaneous APRA injections (5mg). We hypothesized that APRA treatment would lead to thickening of the intestinal mucosa, intestinal lengthening, reduced bowel dilatation and reduced intestinal motility. Therefore, MRI scans of the abdomen, incl. cine sequences, after oral intake of a mannitol solution (600mL) were performed at baseline and at 4W, 24W and 48W of treatment. Morphology parameters were measured on static MRI sequences; GI Quant software was used to quantify motility on cine MRI sequences. Data are presented as median (IQR). Nominal p-values are calculated using Wilcoxon matched-pairs signed rank tests with significance set at 0.05.

Results

Nine pts were included and comprise the full study population. While the numerically increased colon length failed to reach significance, small bowel length increased significantly from 29.7 to 40.7 cm (p=0.012) at 48W. Duodenal wall thickness increased by 0.8 (0.2;1.2) mm (p=0.020). There were no diameter changes in the small bowel nor colon. Changes in motility were evaluated using data from 7 pts, due to missing data. Over time, small bowel motility gradually reduced, albeit not significant. Motility in the proximal colon was significantly reduced at 48W. In the distal colon, decreased motility was observed at 4W and 24W, but returned to baseline level at 48W.

Conclusion

Using static and cine MRI sequences in pts with SBS-IF-CIC, STARS Nutrition shows that APRA treatment was associated with small bowel lengthening and increased duodenal wall thickness suggesting an intestinotrophic effect. Both effects may contribute to an increased surface area for absorption. The reduced motility, especially in the proximal colon may reduce transit time, allowing more time for absorption of nutrients, fluids and electrolytes; and reduced fecal output. Whether bowel lengthening results from a direct effect of APRA vs. changes in motility with passive elongation is subject of further investigation.

Disclosure

Astrid Verbiest, Mark Krogh Hvistendahl, Ragna Vanslembrouck, Ronald Peeters, Riccardo Sartoris – nothing to declare.
Palle Bekker Jeppesen – received grants/research support/honoraria or consultation fees from Agomab, Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast, Ferring, Fresenius Kabi, GLyPharma, Naia Pharma, NPS Pharmaceuticals, NorthSea Therapeutics, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectivBio and Zealand Pharma.
Francisca Joly – has received grants/research support/honoraria or consultation fees from Agomab, Baxter, Fresenius Kabi, Nestlé Health Sciences, BBraun, Theradial, Mayoli, Biocodex, mobile3e Consulting, Carembouche, NPS Pharmaceuticals, NorthSea Therapeutics, Shire, Takeda, Therachon, VectivBio and Zealand Pharma.
Tim Vanuytsel – has served on the speaker bureau for Abbott, Agomab, Baxter, Biocodex, Dr. Falk Pharma, Fresenius Kabi, Ipsen, Menarini, Microbiotica, MyHealth, Remedus, Takeda, Truvion, VectivBio and Zealand Pharma. TV has provided clinical advice to Baxter, Danone, Dr. Falk Pharma, MyHealth, NorthSea Therapeutics, Shire, Therachon, Takeda, VectivBio, Zealand Pharma. TV has received research grants from Danone, MyHealth, Takeda and VectivBio.
Federico Bolognani, Carrie Li and Nader N. Youssef – employees of VectivBio/Ironwood.

This research was supported by VectivBio AG/Ironwood.

MAGNETIC RESONANCE IMAGING (MRI) SHOWS CHANGES IN BOWEL MORPHOLOGY AND MOTILITY IN SHORT BOWEL SYNDROME WITH INTESTINAL FAILURE (SBS-IF) AND COLON-IN-CONTINUITY (CIC) AFTER TREATMENT WITH THE LONG-ACTING GLUCAGON-LIKE PEPTIDE-2 (GLP-2) ANALOG APRAGLUTIDE

Astrid Verbiest 1, Alex Menys 2, Ragna Vanslembrouck 3, Ronald Peeters 3, Riccardo Sartoris 4, Mark Krogh Hvistendahl 5, Federico Bolognani 6, Carrie Li 6, Nader N. Youssef 6, Palle Bekker Jeppesen 5, Francisca Joly 4, Tim Vanuytsel 1

1 University of Leuven, Leuven, Belgium|||University Hospitals Leuven, Leuven, Belgium

2 Motilent, London, United Kingdom

3 University Hospitals Leuven, Leuven, Belgium

4 Hôpital Beaujon, Clichy, France

5 Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

6 VectivBio/Ironwood, Basel, Switzerland

Event

UEG Week Vienna 2024

Topics

Mechanisms & Personalised Medicine Neurogastroenterology & Motility Radiology & Imaging Small Intestine & Nutrition

Submission format

Abstract

Session

Short bowel syndrome

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Introduction

Concerns regarding colorectal cancer in short bowel syndrome (SBS) patients receiving teduglutide (TED) treatment have led to the recommendation of colonoscopy for screening and surveillance.^1,2 While there are reports of new small bowel polyps in TED patients, data on small bowel cancer risk and surveillance are lacking.^3,4 This study aims to evaluate the feasibility and effectiveness of using double-balloon enteroscopy (DBE) for surveillance in SBS patients undergoing TED treatment.

Aims & Methods

Data from patients with SBS in TED treatment who underwent DBE within a year of starting TED at a tertiary referral center for enteroscopy between December 2019 and October 2023 were collected. The primary endpoints were technical success, adverse events, and total enteroscopy rates. Secondary endpoints included the incidence of small bowel polyps and residual small bowel length measurement.

Results

Nine patients (7 female, median age 65.5, IQR 58-79) with SBS (22% type 1, 55.6% type 2, 22.2% type 3-SBS) underwent DBE (10 anterograde, 2 retrograde) under procedural sedation. Crohn’s disease (33.3%) and post-surgical complications (33.3%) were the most frequent causes of SBS. The median interval from TED prescription to DBE surveillance was 9.1 months (IQR 3.2-32.9). The median depth of maximal insertion was 85 cm (IQR 50-187). No adverse events occurred during all the procedures. The total enteroscopy rate was 75% (80% [8/10] of anterograde DBEs, 50% [1/2] of retrograde DBEs). Panenteric DBE allowed the estimation of small bowel residual length in all cases (2/2) where this important clinical information was unknown and revealed a different residual small bowel length compared to surgery in 44% of patients. No small bowel malignancies were detected during the study period.

Conclusion

DBE surveillance for small bowel malignancy in SBS patients undergoing TED treatment is feasible and effective. Total enteroscopy can be frequently achieved with a single endoscopy in these patients, allowing easy oncologic surveillance.

References

1. Revestive (teduglutide). Summary of product characteristics. Takeda; August 2022. Accessed 23 March 2024. https://www. medicines.org.uk/emc/product/3382/smpc
2. Pironi L, Allard JP, Joly F, et al. Use of teduglutide in adults with short bowel syndrome-associated intestinal failure. Nutr Clin Pract 2024;39:141-153.
3. Pevny S, Pape UF, Elezkurtaj S, et al. De Novo Development of Distal Jejunal and Duodenal Adenomas After 41 Months of Teduglutide Treatment in a Patient With Short-Bowel Syndrome: A Case Report. JPEN J Parenter Enteral Nutr 2021;45:652-656.
4. Ukleja A, Alkhairi B, Bejarano P, et al. De Novo Development of Hamartomatous Duodenal Polyps in a Patient With Short Bowel Syndrome During Teduglutide Therapy: A Case Report. JPEN J Parenter Enteral Nutr 2018;42:658-660.

ENDOSCOPIC SMALL BOWEL SURVEILLANCE IN PATIENTS WITH SHORT BOWEL SYNDROME IN TREATMENT WITH TEDUGLUTIDE

Andrea Sorge 1, Lucia Scaramella 2, Veronica Smania 3, Nicoletta Nandi 3, Andrea Costantino 2, Marco Michelon 3, Tommaso Pessarelli 3, Maurizio Vecchi 4, Gian Eugenio Tontini 4, Luca Elli 5

1 University of Milan, Milan, Italy|||Ghent University Hospital, Ghent, Belgium

2 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

3 University of Milan, Milan, Italy

4 Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico University of Milan, Milan, Italy|||University of Milan, Milan, Italy

5 Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico University of Milan, Milan, Italy

Conference

UEG Week Vienna 2024

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

SMALL INTESTINAL (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Presentation

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EFFICACY AND SAFETY OF APRAGLUTIDE ONCE-WEEKLY IN PATIENTS WITH SHORT BOWEL SYNDROME AND INTESTINAL FAILURE (SBS-IF): RESULTS FROM THE STARS STUDY – A GLOBAL PHASE 3 DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL

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Introduction

In SBS-IF, patients (pts) depend on parenteral support (PS) to meet nutritional and/or fluid requirements. Apraglutide (APRA) is a long-acting novel GLP-2 analogue dosed once-weekly that stimulates intestinal adaptation, with the potential to reduce PS requirements. This phase 3 trial assessed the efficacy and safety of APRA vs placebo (PBO) in adult pts with SBS-IF.

Aims & Methods

In this phase 3 double-blind, PBO-controlled trial (NCT04627025) conducted in 73 centres and 18 countries, 164 pts were randomized 2:1 to once-weekly subcutaneous APRA (5 mg if pt ≥50 kg, 2.5 mg if pt <50 kg) or PBO, stratified by intestinal anatomy (stoma or colon-in-continuity [CIC]). The primary endpoint was relative change from baseline (BL) in weekly PS volume at Week (Wk) 24. Key secondary endpoints at Wk 24 were reduction of additional ≥1 day/Wk off PS from BL, and in the stoma subgroup, relative change from BL in weekly PS volume. Two other key secondary endpoints at Wk 48 in the CIC subgroup were reduction of ≥1 day/Wk off PS, and percentage of pts reaching total enteral autonomy. Wk 24 clinical responders were defined as proportion of pts with ≥20% PS reduction at Wks 20 and 24. Adverse events (AEs) were collected.

Results

A total of 163 dosed pts (80 stoma; 83 CIC),155 (95%) completed the study. BL demographics and mean BL weekly PS volume (APRA 13.1 L; PBO 12.9 L) were similar in both arms. At Wk 24, APRA-treated pts had a significantly larger reduction from BL in weekly PS volume vs PBO (APRA -25.5%; PBO -12.5%; p=0.001); both stoma and CIC subgroups demonstrated comparable treatment effects. In pts with stoma, the relative reduction from BL to Wk 24 in weekly PS volume in APRA pts vs PBO was statistically significant (-25.6% vs -7.8%; p<0.001) (Table 1). In pts with CIC, there was a numerical benefit in APRA that did not reach statistical significance (APRA -25.2%; PBO -17.6%; nominal p=0.179). In the overall population, statistically significant PS reductions from BL were seen from Wk 8 onward. A significantly higher proportion of APRA pts achieved a reduction of ≥1 day/Wk off PS at Wk 24 (APRA 43.0%; PBO 27.5%; p=0.040). At Wk 48 in the CIC subgroup, 51.8% of APRA vs 44.4% of PBO-treated pts achieved ≥1 day/wk off PS (p=0.348), and enteral autonomy was reached in 7 of 56 (12.5%) APRA vs 2 of 27 (7.4%). APRA was well tolerated. Of 110 APRA-treated pts, only 4 (3.6%) discontinued APRA due to an AE, vs 1 of 53 (1.9%) PBO-treated pts.

Conclusion

APRA is the first once-weekly GLP-2 analogue to demonstrate efficacy in a phase 3 trial in SBS-IF. At Wk 24, APRA demonstrated significantly greater relative reductions in weekly PS volume from BL and a higher proportion of pts achieved an additional ≥1 day off PS, with comparable treatment effects in pts with stoma or CIC. APRA showed a favourable safety profile consistent with prior APRA studies in SBS-IF.

n for the first key secondary is observed value and the percentage, difference in percentages and its p-value is based on results of multiple imputations. *nominal p-value. APRA, apraglutide; BL, baseline; CI, confidence interval; LSM, least square mean; PBO, placebo; PS, parenteral support; SBS-IF, short bowel syndrome and intestinal failure.
Endpoint	Population	Apraglutide (n=110)	Placebo (n=53)	APRA vs PBO Difference [LSM or % (95% CI)]	p-value
Primary Endpoint		LSM or n (%)
Relative % change from BL in actual PS weekly volume at Wk 24, Least Square Mean (LSM)	Overall	-25.5	-12.5	-13.0 (-20.9, -5.0)	0.001
Key Secondary Endpoints
Percentage of subjects achieving a reduction of ≥1 day/wk off PS from BL at Wk 24, n (%) *	Overall	46 (43.0)	14 (27.5)	15.6 (0.7, 30.5)	0.040
Relative % change from BL in actual PS weekly volume at Wk 24, mean	Stoma (n=80)	-25.6	-7.8	-17.8 (-28.4, -7.3)	<0.001
Percentage of subjects achieving a reduction of ≥1 day/wk off PS from BL at Wk 48, n (%)	CIC (n=83)	29/56 (51.8)	12/27 (44.4)	7.3 (-16.4, 29.8)	0.348
Subjects reaching enteral autonomy at Wk 48, n (%)	CIC (n=83)	7/56 (12.5)	2/27 (7.4)	5.1 (-12.9, 18.5)	0.387
Other Secondary Endpoint Clinical responders at Week 24 (≥20% PS reduction at both Wks 20 and 24), n (%)	Overall	47 (42.7)	11 (20.8)	22.0 (7.7, 36.2)	0.003**

Disclosure

FJ: Research funding from Takeda Pharma, VectivBio, Zealand, Baxter, Mobile3esolutions, Carembouche Consultant or advisor for Takeda, VectivBio, Ironwood; NorthSea Therapeutics, Hamni, Zealand, Mobile3esolutions, Carembouche. Lecturer for Baxter, BBraun, Fresenius Kabi, Janssen, Theradial; TV: Research Grants for Danone, MyHealth, Takeda, VectivBio. Consultancy for Baxter, BMS, Dr. Falk Pharma, Hanmi Pharm, North Sea Therapeutics, Takeda, Truvion, VectivBio, Zealand Pharma. Lecturer for Abbott, Baxter, Biocodex, Dr. Falk Pharma, Fresenius Kabi, Ipsen, Menarini, MyHealth, Remedus, Takeda, Truvion, VectivBio. DK: Consultant or advisor forTakeda Pharma, VectivBio, OWYN; SL: Investigator-initiated/unrestricted research grants from Fresenius Kabi, Baxter and Takeda. Honoraria and/or educational support from Takeda, Zealand, VectivBio, Fresenius Kabi, B Braun, Baxter, Northsea. KT: Board Member/Advisory Panel/Speaker for Abbott Nutrition Health Institute, Nutricia North America,Takeda Pharmaceuticals, VectivBio – now part of Ironwood Pharmaceuticals, Inc; PJ: Honoraria, educational and/or grants from Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast A/S, Ferring Pharmaceuticals, Fresenius Kabi, GlyPharma Therapeutic, Hanmi Pharmaceuticals, Ironwood, Naia Pharmaceuticals, NPS Pharmaceuticals, Protara Therapeutics, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectivBio AG, Zealand Pharma A/S; NNY, CL, RS, IS, SH: Ironwood employees; FB: Ironwood consultant; KI: Grant support from Takeda Pharma, VectivBio, NorthSea Therapeutics. Consultant or advisor for Takeda Pharma, VectivBio, Northsea Therapeutics, Hanmi Pharmaceuticals. Speaker or member of speakers bureau for Takeda Pharma.

EFFICACY AND SAFETY OF APRAGLUTIDE ONCE-WEEKLY IN PATIENTS WITH SHORT BOWEL SYNDROME AND INTESTINAL FAILURE (SBS-IF): RESULTS FROM THE STARS STUDY – A GLOBAL PHASE 3 DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL

Francisca Joly 1, Tim Vanuytsel 2, Donald Kirby 3, Simon Lal 4, Kelly Tappenden 5, Palle Bekker Jeppesen 6, Nader N. Youssef 7, Carrie Li 7, Reda Sheik 7, Isabelle Statovci 7, Susanna Huh 8, Federico Bolognani 7, Kishore Iyer 9

1 Beaujon Hospital Service de Gastroenterologie, Clichy, France

2 KU Leuven, Leuven, Belgium

3 Cleveland Clinic, Cleveland, United States

4 University of Manchester, Manchester, United Kingdom

5 The University of Utah, Salt Lake City, United States

6 Rigshospitalet, Copenhagen, Denmark

7 Ironwood Pharmaceuticals, Basel, Switzerland

8 Ironwood Pharmaceuticals, Boston, United States

9 Mount Sinai Medical Center, New York, United States

Event

UEG Week Vienna 2024

Topics

Mechanisms & Personalised Medicine Neurogastroenterology & Motility Radiology & Imaging Small Intestine & Nutrition

Submission format

Abstract

Session

Short bowel syndrome

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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