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Introduction

Janus kinase inhibitors (JAKi) are small molecule drugs with demonstrated efficacy in inflammatory bowel disease (IBD). However, widespread utilisation may be hindered by safety concerns.

Aims & Methods

The aim of this study was to assess the risk-benefit perceptions, attitudes, and clinical practices of those using JAKi to treat IBD. A prospective, cross-sectional study was conducted using a 23-item electronic survey, which was distributed to ECCO members and delegates of the 18th Congress of ECCO, 2023, held in Copenhagen, Denmark.

Results

There were 385 respondents from 48 countries; 72% were based in tertiary referral centres and 50% were gastroenterologists with ≥10 years’ experience. JAKi were rarely used first line (8%) but were commonly used outside market authorisation (31%). Many (17%) were unconfident discussing JAKi risk-benefit profile and 7% had never prescribed JAKi despite consulting >100 unique IBD patients/year. If venous thromboembolism risks were present, 15% preferentially referred for surgery than initiate JAKi; 21% would do this even if the patient was already anticoagulated. IBD subspecialists with full GI accreditation were less likely to refer to surgery over JAKi initiation, OR 0.40 (95% CI 0.17-0.85) p=0.02. For patients relapsing on dose-reduction, 8% would switch treatment rather than dose-escalate. Conversely, 45% felt that cardiovascular safety concerns from post-marketing studies were irrelevant to IBD. Despite lack of detailed, long-term safety data, safety profiles of novel JAK1-selective drugs were perceived to be favourable to tofacitinib by most (62%).

Conclusion

The study provides unique insights from an international cohort of experienced IBD clinicians and indicates that while clinical practice appears to be in keeping with international guidance, a significant minority remain deterred by safety concerns.

Disclosure

SH served as a speaker, a consultant, and/or an advisory board member for Pfizer, Janssen, AbbVie, and Takeda. Travel grants received from Ferring, Falk Pharma, and Pharmacosmos.
PMI has received lecture fees from AbbVie, Warner Chilcott, Ferring, Falk Pharma, Takeda, MSD, Johnson and Johnson, Shire and Pfizer. Financial support for research: MSD, Takeda, and Pfizer. Advisory fees: AbbVie, Warner Chilcott, Takeda, MSD, Vifor Pharma, Pharmacosmos, Topivert, Genentech, Hospira, Samsung Bioepis.
MAS served as a speaker, a consultant, and/or an advisory board member for Sandoz, Janssen, Takeda, MSD, Falk, AbbVie, Bristol Myers Squibb, Galapagos, Pfizer, and Samsung Bioepis.

JAK INHIBITORS FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE: RESULTS OF AN INTERNATIONAL SURVEY OF PERCEPTIONS, ATTITUDES, AND CLINICAL PRACTICE

Sailish Honap 1, Peter Irving 2, Mark Samaan 3

1 St George's University Hospitals NHS Foundation Trust, London, United Kingdom|||King's College London, London, United Kingdom

2 King's College London, London, United Kingdom|||Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom

3 Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

UEG Presentation

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How to create AI for Barrett's oesophagus and how to integrate it in its management

Jacques J. Bergman 1, Fons van der Sommen 2

1 Academic Medical Centre - Gastroenterology & Hepatology, Academic Medical Centre; Amsterdam/NL, Amsterdam, Netherlands

2 Eindhoven University of Technology, Eindhoven, Netherlands

Event

UEG Week Copenhagen 2023

Topics

Education & Training Endoscopy Histopathology

Session

Disease primer: AI - the new standard in endoscopy and pathology

Published

2023

UEG Presentation

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Gathering intelligence to improve long-term outcomes in ulcerative colitis: new evidence (Takeda) (Complete Session)

Alessandro Armuzzi 1, Fernando Magro 2, Bruce E. Sands 3

1 IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy

2 Centro Hospitalar São João, Amadora, Portugal

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

Publisher

Takeda Pharmaceuticals International AG

Event

UEG Week Copenhagen 2023

Session

Gathering intelligence to improve long-term outcomes in ulcerative colitis: new evidence (Takeda)

Published

2023

UEG Presentation

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MIR-21-5P DRIVES NASH-ASSOCIATED HEPATOCARCINOGENESIS

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Introduction

Non-alcoholic fatty liver disease (NAFLD) often advances to more severe stages, namely steatohepatitis (NASH), and may further progress towards hepatocellular carcinoma (HCC). Still, the cellular and molecular mechanisms governing disease progression - and that may be ammendable to therapeutic intervention - remain elusive.

Aims & Methods

Here, we evaluated the role of hsa-miRNA-21-5p in NASH-related hepatocarcinogenesis.
Hepatic hsa-miR-21-5p expression was evaluated in two cohorts of patients with biopsy-proven NAFLD (n=199) or HCC (n=366 HCC and n=11 NAFLD-HCC). Serum/liver metabolomic profiles were correlated with hsa-miR-21-5p in NAFLD obese patients. Wild-type (WT) and Mir21 KO mice were fed a choline-deficient, amino acid-defined (CDAA) diet for 32 weeks to induce NASH; and for 66 weeks to induce NASH-HCC.

Results

Results showed that hsa-miR-21-5p expression increased with NAFLD severity and associated with a hepatic lipotoxic profile in obese patients. CDAA-fed WT mice displayed increased hepatic mmu-miR-21-5p levels and progressively developed NASH and fibrosis, with livers presenting macroscopically discernible pre-neoplastic nodules, hyperplastic foci and deregulated cancer-related pathways. Mir21 KO mice displayed increased peroxisome-proliferator activated receptor alpha (PPARalpha) protein levels, augmented mitochondrial activity, reduced liver injury and NAS below the threshold for NASH diagnosis. Further, the pro-inflammatory/fibrogenic milieu was reduced. Mir21 KO mice presented with a lower number of pre-neoplastic nodules, impaired hepatocyte proliferation and downgraded oncogenic signaling, thus being protected from NASH-related carcinogenesis. The hsa-miRNA-21-5p/PPARalpha pathway was similarly deregulated in patients with HCC or NASH-related HCC, correlating with HCC markers and worse prognosis.

Conclusion

In conclusion, hsa-miR-21-5p is a key inducer of whole-spectrum NAFLD progression, from simple steatosis to NASH and NASH-associated carcinogenesis. Inhibition of hsa-miR-21-5p, leading to a pro-metabolomic profile, might constitute an appealing therapeutic approach to ameliorate NASH and prevent progression towards HCC (EXPL/MED-OUT/1317/2021, FCT, Portugal).

MIR-21-5P DRIVES NASH-ASSOCIATED HEPATOCARCINOGENESIS

Pedro M. Rodrigues 1, Marta Bento Afonso 2, André Lopes Simão 2, Tawhidul Islam 2, Maria Manuela Gaspar 2, Colm J. O’Rourke 3, Monika Lewinska 3, Jesper B. Andersen 3, Enara Arretxe 4, Cristina Alonso 4, Álvaro Santos-Laso 5, Laura Izquierdo-Sanchez 6, Raúl Jimenez-Agüero 5, Emma Eizaguirre 5, Luis Bujanda 7, Maria J. Pareja 8, Carina Prip-Buus 9, Jesús M. Bañales 10, Cecília Maria Pereira Rodrigues 2, Rui Castro 2

1 Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal|||Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain|||Centre for the Study of Liver and Gastrointes

2 Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

3 Biotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

4 OWL Metabolomics, Derio, Spain

5 Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain

6 Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal|||Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain

7 Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain|||Centre for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain

8 Hospital Juan Ramón Jiménez, Huelva, Spain

9 Université Paris Descartes UMR-S 1016, Institut Cochin, Paris, France

10 Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain|||Centre for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain|||IKERBASQUE, Basque Foundation

Event

UEG Week Copenhagen 2023

Topics

Colorectal Digestive Oncology Hepatobiliary Mechanisms & Personalised Medicine Pancreas

Submission format

Abstract

Session

Carcinogenesis revisited

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

UEG Presentation

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Panel discussion: Is it a diverticular disease?

Eva Angenete 1, Alessandro Armuzzi 2, Giovanni Barbara 3

1 University Hospital Gothenburg, Gothenburg, Sweden

2 IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy

3 University of Bologna, Bologna, Italy

Event

UEG Week Copenhagen 2023

Topics

Colorectal Neurogastroenterology & Motility Surgery

Session

Is it a diverticular disease?

Published

2023

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Introduction

Gastric submucosal tumors (SMTs) are elevated lesions originating from below the gastric mucosal layer. Pathological types of SMTs include stromal tumors, leiomyomas, lipomas, etc., with stromal tumors being the most common¹. Endoscopic full-thickness resection (EFTR) has gradually become the main treatment modality for SMTs ². However, in order to completely remove lesions involving the submucosal and deeper layers, EFTR often involves intentional perforation during the procedure. Therefore, successful closure of the full-thickness defect after the procedure is crucial to prevent serious complications such as pneumothorax and pneumoperitoneum³. Currently, availabloe techniques for the full-thickness GI wall defects closure includes metal clip closure, nylon suture purse-string closure, Over-The-Scope-Clip system (OTSC), and the OverStitch suture system ^4-5. However, due to variations in endoscopic center equipment, individual physician skills, and patient economic conditions, most of the suture devices are not widely available including in China. Using metal clips alone may sometimes be insufficient for closing the large GI defects, while the purse-string suture technique can be relatively cumbersome.

Aims & Methods

The aim of this study was to evaluate the safety and efficacy of the long transparent cap suturing technique for the closure of large endoscopic full-thickness resection (EFTR) defects. A total of 62 patients who underwent EFTR for their large gastric submucosal tumors at the First Affiliated Hospital of Zhengzhou University between January 2017 and March 2023 were included in this study. The novel long transparent cap suturing technique was used for EFTR defect closure in all the patients.

Results

The procedure technical success rate was 100%. The median tumor size was 1.5 cm (range: 0.6-6.5 cm), and the median number of metal clips used was 7 (range: 4-14). The median EFTR procedure time was 53.5 minutes (range: 22-136 minutes), and the median suturing time was 14 minutes (range: 3-45 minutes). The median length of postoperative hospital stay was 4.5 days (range: 3-7 days). Postoperative complications including bleeding occured in 1 case, fever in 3 cases, and abdominal pain in 2 cases. During the median 29 months (range: 7-79 months) of follow up, no residual lesions, tumor recurrence, or metastasis were detected, and no formation of digestive tract fistulas or sinuses was observed.

Conclusion

The long transparent cap suturing technique is a simple, safe, and effective method for wound closure after EFTR. It is beneficial for clinical application and widespread use.

References

1 Sharzehi K, Sethi A, Savides T. Aga clinical practice update on management of subepithelial lesions encountered during routine endoscopy: Expert review. Clin Gastroenterol Hepatol 2022; 20: 2435-43.e4.
2 Liu S, Zhou X, Yao Y, Shi K, Yu M, Ji F. Resection of the gastric submucosal tumor (g-smt) originating from the muscularis propria layer: Comparison of efficacy, patients' tolerability, and clinical outcomes between endoscopic full-thickness resection and surgical resection. Surg Endosc 2020; 34: 4053-64.
3 Zhou PH, Yao LQ, Qin XY et al. Endoscopic full-thickness resection without laparoscopic assistance for gastric submucosal tumors originated from the muscularis propria. Surg Endosc 2011; 25: 2926-31.
4 Verlaan T, Voermans RP, van Berge Henegouwen MI, Bemelman WA, Fockens P. Endoscopic closure of acute perforations of the gi tract: A systematic review of the literature. Gastrointest Endosc 2014; 82: 618-28.e5.
5 Shi D, Li R, Chen W et al. Application of novel endoloops to close the defects resulted from endoscopic full-thickness resection with single-channel gastroscope: A multicenter study. Surg Endosc 2017; 31: 837-42.