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ISSN 2050-6406 (Print) : ISSN 2050-6414 (Online)

25th United European Gastroenterology WeekBarcelona 2017

Abstract Issue

October 2017 : Volume 5 : Supplement 1http://ueg.sagepub.com

An international forum for clinical practice and research in gastroenterology

Search and browse the Standards & Guidelines Repository at www.ueg.eu/guidelines

UEG and leading European gastroenterological societies concerned with digestive health help you to provide your patients with the best care options

You are looking for…evidence-based guidelines clinical practice guidelinesconsensus guidance for your daily practiceclinical standards position papers standard protocols…in these fields of digestive health?

Digestive oncologyEndoscopyGut microbiotaHepatobiliaryHistopathology

IBDNeurogastroenterology & motilityOesophagusPaediatricsPancreas

Primary careRadiology & imagingSmall intestine & nutritionStomach & H. pyloriSurgery

25th UEG Week 2017

Barcelona, Spain, October 2017

Accepted abstracts available online at:https://www.ueg.eu/publications/abstractbook

www.ueg.eu/education/libraryhttp://ueg.sagepub.com

Disclaimer: United European Gastroenterology (UEG) is not responsible for errors or omissions in the abstracts. Thisabstract book was finalised on September 12, 2017, any changes received after this date have not been incorporated.

Changes to presenters received after August 8 have been included in the online version of the programme and can be

obtained at: www.ueg.eu/education/library.

Disclosure Policy: UEG is committed to ensuring scientific rigour and objectivity in all of its educational activities. Theseinclude all aspects of the educational programme at UEG Week including those that are directly and jointly sponsored

activities.

All presenters, whether invited Faculty or abstract presenters, are required to disclose to those organising and attending

meetings any relevant financial or other relationship that may lead to a potential bias. UEG reserves the right to review

the information disclosed for potential conflicts of interest. Please note that the sole responsibility for the content of each

presentation lies with the presenting author.

The UEG Scientific Committee requires all presenters to disclose any financial relationship with or any advisory role in the

Biomedical Industry and the Biomedical Technology Industry during the past two years. These and any other potential

conflicts of interest should be disclosed during introductory comments to the presentation. Invited speakers and oral

abstract presenters are requested to disclose potential conflicts of interest on a PowerPoint slide to be shown imme-

diately at the beginning of the presentation. Poster presenters are requested to disclose potential conflicts of interest at

the bottom of their poster.

Conflicts of interest may exist through a financial relationship or when the individual has the opportunity to influence the

content of a presentation, and can involve grants, honoraria, shares, paid positions on advisory boards, etc. Conflicts of

interest are frequent and expected, and do not preclude an individual from giving a presentation providing the conflict is

disclosed. If there is any doubt about the relevance of a potential conflict of interest UEG requires all presenters to err on

the safe side and to disclose it.

www.ueg.eu/education/libraryhttp://ueg.sagepub.comwww.ueg.eu/education/library

Aims and scopeLaunched in 2013, United European Gastroenterology Journal is the official Journal of United European Gastroenterology (UEG), a professional non-profit organisation combining all the leading European societies concerned with digestive disease. UEG’s member societies represent over 22,000specialists working across medicine, surgery, paediatrics, GI oncology and endoscopy, which makes UEG a unique platform for collaboration andthe exchange of knowledge.

United European Gastroenterology Journal provides an international forum for research in gastroenterology, publishing original articles whichdescribe basic research, translational and clinical studies of interest to gastroenterologists and researchers in related fields. Articles from acrossall fields of gastroenterology are be welcomed by the Editor-in-Chief, including luminal, liver and pancreatic diseases, gastrointestinal surgery,gastrointestinal oncology, paediatric gastroenterology and nutrition as well as endoscopy.

Published article types include original research, reviews, guidelines papers and news items. The journal is a member of the Committee onPublication Ethics (COPE).

2017 annual subscription ratesUnited European Gastroenterology Journal ISSN: 2050-6406 (print) 2050-6414 (online) is published in February, April, June, August, October andDecember by SAGE Publications (London, Thousand Oaks, CA, New Delhi, Singapore, Washington DC and Melbourne).

Annual subscription (2017) including postage: Institutional Rate (combined print and electronic) £786/US$1456. Note VAT might be applicable atthe appropriate local rate. Visit sagepublishing.com for more details. To activate your subscription (institutions only) visit online.sagepub.comonline. Abstracts, tables of contents and contents alerts are available on this site free of charge for all. Student discounts, single issue rates andadvertising details are available from SAGE Publications Ltd, 1 Oliver’s Yard, 55 City Road, London EC1Y 1SP, UK, tel. +44 (0)20 7324 8500,email: [email protected] and in North America, SAGE Publications Inc, PO Box 5096, Thousand Oaks, CA 91320, USA.

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Peer review policyUnited European Gastroenterology Journal operates a conventional single-blind reviewing policy in which the reviewer’s name is always concealedfrom the submitting author. Papers will be sent for anonymous review by at least two reviewers who will either be members of the Editorial Boardor others of similar standing in the field. The Editors’ decision is final and no correspondence can be entered into concerning manuscriptsconsidered unsuitable for publication in United European Gastroenterology Journal. All correspondence, including notification of the Editorsdecision and requests for revisions, will be sent by email.

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! UEG 2017

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Printed on acid-free paper by Page Bros., Norwich, UK.

EditorJan Tack, University of Leuven, Belgium

Associate EditorsTim Greten, NIH, USA

Oliver Pech, St John of God Hospital, Regensburg, Germany

Janneke van der Woude, Erasmus MC, the Netherlands

Editorial BoardAlberto Arezzo, MD, PhD, Associate Professor of Surgery,

Surgeon, specialised in Colorectal surgery and operative

endoscopy, University Hospital of Torino, Italy

David Armstrong, MA, MB BChir, FRCPC, FRCP (UK), FACG,

AGAF, Professor of Medicine, McMaster University,

Gastroenterologist, specialising in Upper GI Disorders &

Nutrition, Hamilton Health Sciences, Canada

Michael Bourke, MBBS, FRACP, Professor of Medicine,

University of Sydney, Director Gastrointestinal Endoscopy,

Westmead Hospital

Guido Costamagna, MD, MS, Professor of Surgery, Surgeon

and Gastroenterologist, Catholic University of the Sacred

Heart, Rome

Carlo Di Lorenzo, MD, Professor of Pediatrics, Pediatric gas-

troenterologist, specialized in motility and functional GI

disorders in children, Nationwide Children’s Hospital, The

Ohio State University

Douglas A. Drossman, MD, Professor Emeritus of Medicine

and Psychiatry, Co-Director Emeritus Center for Functional

GI and Motility Disorders, University of North Carolina,

Drossman Center for Education and Practice of

Biopsychosocial Care, Drossman Gastroenterology PLLC,

Chapel Hill, NC USA

Johanna C Escher, M.D., Ph.D., Professor in Pediatrics,

Pediatric IBD, Head of Department of Pediatric

Gastroenterology, Erasmus Universiteit, Erasmus Medical

Center, Rotterdam

Ronnie Fass, MD, Professor of Medicine, Case Western Reserve

University, Chairman, Division of Gastroenterology and

Hepatology, Director, Esophageal and Swallowing center,

MetroHealth Medical Center, Cleveland, Ohio USA

Richard Hunt, MD, FRCP, FRCP (C), FACG, FAGA, Professor

Emeritus, Division of Gastroenterology Gastroenterologist

McMaster University, Hamilton

Michael P. Jones, BSc(Hons), PhD, A.STAT, C.STAT, Professor

of Psychology and Associate Dean (Research), Statistician

specialising in functional gastrointestinal epidemiology

and psychology, Faculty of Human Sciences, Macquarie

University, North Ryde, NSW, Australia

John Kellow, MD, Associate Professor and Head of the

Discipline of Medicine, Gastroenterologist, Northern

Clinical School, University of Sydney

Markus M. Lerch, MD, FRCP, Professor of Medicine,

Gastroenterologist, Endocrinologist, Specialized in diseases

of the pancreas, University Medicine Greifswald, Germany

Lars Lundell, MD, PhD, Professor of Surgery, Specialist in Upper

Abdominal Surgery Gastrocentrum, Centre for Digestive

Diseases Karolinska University Hospital, Stockholm

Hendrik Manner, MD, PhD, Gastroenterologist, specialized in

interventional endoscopy, Helios HSK Hospital Wiesbaden,

Teaching Hospital of the University Medicine of Mainz, Mainz

Helmut Neumann, MD, PhD, Professor of Medicine, Consultant

Internal Medicine and Gastroenterology, Specialized in

diagnostic and therapeutic endoscopy and molecular ima-

ging, University of Erlanden-Nuremberg, Germany

Stefan Schreiber, MD, Professor of Internal Medicine and

Gastroenterology, Research focus on etiology of chronic

Inflammation and clinical pathophysiology of IBD,

Christian-Albrechts-University Kiel, University Hospital

Schleswig Holstein

Vincenzo Stanghellini, MD, Professor of Medicine,

Gastroenterologist, specialized in GI Motility and Functional

Digestive Syndromes, University Hospital Bologna, Italy

Jaap Stoker, MD, Professor of Radiology, Radiologist, specia-

lised in gastrointestinal disease, Academic Medical Centre,

University of Amsterdam

Hidekazu Suzuki, MD, PhD, FACG, AGAF, RFF, Professor,

Gastroenterologist, Medical Education Center, Keio

University School of Medicine, Tokyo

Michael Vieth, MD , PhD, Professor of Pathology, Pathologist,

special interest in GI-tract, University of Bayreuth, Germany

Michael B Wallace, MD MPH, Professor of Medicine,

Gastroenterologist specializing in advance diagnostic and

therapeutic endoscopy, Mayo Clinic, Jacksonville, Florida, USA

Heiner Wedemeyer, MD, Professor of Medicine,

Gastroenterologist, specialized in Hepatology, Dept. of

Gastroenterology, Hepatology and Endocrinology,

Hannover Medical School

Frank Zerbib, MD, PhD, Professor of Gastroenterology,

Specialized in motility disorders and reflux disease,

Bordeaux University Hospital, France

PH Zhou, MD, PhD, Associate Professor of General Surgery,

Endoscopy Center Zhongsgan Hospital, Fudan University,

Shanghai, China

Letter of Thanks for UEG Week 2017 Reviewers

Dear Colleagues,

On behalf of the UEG Scientific Committee, I would like to take this opportunity to thank you most sincerely foryour contribution as an abstract reviewer for the original programme of the 25th UEG Week Barcelona 2017.

The abstract reviewing process has been again very important this year, with a number of innovations intro-duced to improve especially the poster abstract presentations.

I know just how much time and effort reviewing abstracts takes, but without your expertise we would not havethe quality that I believe we have achieved in the free paper and poster sessions, and UEG Week would not be thetop international digestive diseases meeting that it has become today. Thank you!

We received a total of 3438 abstracts for UEG Week Barcelona 2017. In total, 2341 abstracts were accepted,giving an acceptance rate of 68.13%. Of these, 378 abstracts will be delivered as oral presentations and 1963 asposters. I am even more pleased to tell you that standards have again reached a very high level, and we can expectto be exposed to most interesting research and great presentations.

This high volume and high standard confirm that UEG Week is the most important forum at which to presentyour best research. We have received 95 video cases which were formally evaluated by the Scientific Committee forpresentation in Barcelona. As in previous years, late-breaking abstracts have been scored by the ScientificCommittee for presentation in Barcelona.

The quality of reviewing this year was excellent, but if you have any further (positive or negative) comments,please do let us know!

Finally, but most importantly, thanks to all investigators both within and outside Europe who have submittedtheir research to the meeting, and who are clearly contributing to making the 25th UEG Week Barcelona 2017such a great success!

Professor Magnus SimrénChair, UEG Scientific Committee, Barcelona 2017

United European Gastroenterology Journal

2017, Vol. 5(5S) iv

! Author(s) 2017

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DOI: 10.1177/2050640617725665

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Thanks to Partners, Sponsor and Exhibitors

United European Gastroenterology (UEG) gratefully acknowledgesthe support of the following companies and other exhibitors:

This list reflects the status as per 20 July 2017.

Premium Partners

AbbvieFUJIFILMJanssenOlympus Europa SE & Co., KGPfizerTakeda Pharmaceuticals International AG

Major Partners

Allergan Pharmaceuticals International LtdBoehringer Ingelheim Pharma GmbH & Co., KGCELLTRION HEALTHCAREMEDTRONICMSDNorginePENTAX EUROPE GmbHShire International GmbH

General Sponsors and Exhibitors

3D Matrix EMEA B.V3D Systems SimbionixACTIAL FARMACEUTICA SRLAlfasigma S.p.AAlton (Shanghai) Medical Instruments Co., Ltdamg International GmbHAmgenAnkonANREI MEDICALApollo EndosurgeryBayer Consumer HealthBCM Co., LtdBedfont ScientificBeijing Richen-Force HoldingsBHT Hygienetechnik GmbHBiocodexBioGaiaBiohit OyjBiomedal

Boston ScientificBÜHLMANN Laboratories AGCALPRO ASCantelCapsoVisionCasen Recordati S.LCBC GroupCelgene CorporationChangzhou Dahua Group/CitecChoyang MedicalCook MedicalCreo Medical Ltd.Dr. Falk Pharma GmbHDr. Henke Medical Training & EducationELLA-CSEMcision International Inc.EMED SP. Z O. O. SP. K.EndoAid Ltd.EndoClot Plus, Inc.


2017, Vol. 5(5S) v–vi

! Author(s) 2017



DOI: 10.1177/2050640617725666



Endoscopic Ultrasound JournalEndoscopy / ESGE -ThiemeEndoSim Europe GmbHEndoticsErbe Elektromedizin GmbHEurospitalExalenzF. Hoffmann La RocheFerring PharmaceuticalsFinemedix Co., LtdFischer Analysen Instrumente GmbHGE HealthcareGenetic Analysis ASGI SupplyGilead SciencesGrifolsHangzhou AGS MedTech Co., Ltd.Huger Medical Instrument Co., LtdImmundiagnostik AGINFAI GMBHInnovex Medical Co., Ltd.Insitumed GmbHIntercept Pharmaceutical Europe LtdIntromedic Co., Ltd.invendo medical GmbHJiangsu ATE Medical Technology Co., LtdJinshan Science & TechnologyKarger PublishersKARL STORZ GmBH & Co., KgLA LETTRE DE L’HEPATO-

GASTROENTEROLOGUELABORIELeo Medical Co., Ltd.Life Partners EuropeLumendiM.I. Tech Ltd.Mauna Kea TechnologiesMayoly SpindlerMederi Therapeutics Inc.MedifyMedi-Globe GmbH/ Endo-Flex GmbHMEDITALIA S.A.S.Medix BiochemicaMednovamedwork GmbH

Micro-Tech-Europe GmbHMTW-EndoskopieNEXTBIOMEDICAL Co., Ltd.NIKKISONiso Biomed srlNoventureOvesco Endoscopy AGOxford University PressPeter Pflugbeil GmbH Medizinische InstrumentePrecisionBiotics LtdProbiotics International Ltd (Protexin)Prometheus Laboratories Inc.R-BiopharmReckitt BenckiserRobarts Clinical Trials B.V.Samsung BioepisSandhill ScientificSandoz BiopharmaceuticalsShangxian Minimal Invasive Inc.Shenzhen Zhonghe Headway Bio-Sci & Tech Co., LtdShionogi Europe LtdSMART Medical Systems Ltd.SOFAR SPASOLUSCOPESonoScape Medical Corp.Standard Sci-Tech Inc.STEELCO SPASTERISSUMITOMO BAKELITE CO., LTD.Surgical Science Sweden ABTaewoong Medical Co., LtdTEAC Europe GmbHThe LancetThe Standard Co., LtdTillotts Pharma AGTristelUS EndoscopyVital Therapies, Inc.W.L. Gore & Associates GmbHWalz ElektronikWassenburg Medical B.V.WILSON INSTRUMENTS (SHA) Co., LtdWilson Therapeutics ABWisepressZhuji Pengtian Medical Instrument Co., Ltd

vi United European Gastroenterology Journal 5(5S)

Contents

Letter of Thanks for UEG Week 2017 Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iv

Thanks to Partners, Sponsor and Exhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v

UEG Week 2017 Oral Presentations

Monday, October 30, 2017

Opening Session: Part I – Hall 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Opening Session: Part II – Hall 6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Clinical Trials In Crohn’s Disease – Room F3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Fatty Liver Disease: Update 2017 – Room A2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Hot Topics From Latin America – Room A3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Disease Burden In IBD – Room B2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Imaging, Screening And Surveillance Of Colorectal Cancer – Room 7.1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Advanced Endoscopic Treatment Of Upper GI Neoplasia – Room E2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Diagnosis And Management Of Cirrhosis: Unmet Needs – Room E3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Bariatric Surgery, Obesity And Weight Loss – Room B5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Abstracts On Fire: Advances In Endoscopic Resection Of Early Colorectal Neoplasia – Hotspot . . . . . . . . . . 19

Imaging And Endoscopy In IBD – Room A1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Celiac Disease And Wheat-Related Disorder – Room B2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

TSTM Free Paper: New Concepts In Host-Microbiota Crosstalks – Room E4 . . . . . . . . . . . . . . . . . . . . . . . 28

IBS: Searching For Biomarkers – Room 7.1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Advances In Endoscopic Imaging: What Does The Future Hold? – Room E2 . . . . . . . . . . . . . . . . . . . . . . . . 32

Challenges In Pancreatic And Biliary Surgery – Room E3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

Drugs, Liver And Pancreas – Room B5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Clinical Trials In Ulcerative Colitis – Room F2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

Alcoholic Liver Disease: Anything New? – Room A2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

ERCP: When The Going Gets Tough – Room B2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Sporadic And Hereditary Colon Cancer – Room 7.1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

Gluten-Related Disorders – Room E2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

General Hepatology – Room E3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

Upper GI Motility And Brain-Gut Interactions – Room B5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

Tuesday, October 31, 2017

Recurrences After Colorectal Endoscopic Mucosal Resection (EMR)/Endoscopic SubmucosalDissection (ESD): How To Avoid, How To Treat? – Room A1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

Detection And Removal Of Colorectal Polyps: Latest Techniques – Room A3 . . . . . . . . . . . . . . . . . . . . . . . 57

Diagnosis And Treatment Of GORD – Room B2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

TSTM Free Paper: Clinical Implications Of Host Microbiota Interactions – Room E4. . . . . . . . . . . . . . . . . . 62

The Microbiome And IBD – Room 7.1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

Symptom Patterns In Functional GI Disorders – Room E1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

Acute And Chronic Pancreatitis: Risk Factors And Prevention – Room E2. . . . . . . . . . . . . . . . . . . . . . . . . . 71

Progress In Endoscopic Diagnosis – Room E3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

New Insights In Microbiota: Gut And Liver Aspects – Room B5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76

Perianal Fistulising Crohn’s Disease: From Pathophysiology To Management – Room C1 . . . . . . . . . . . . . . . 78

Longterm Management In IBD With Biologics – Room A3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79

Evidence-Based Management Of Barrett’s And Oesophageal Adenocarcinoma – Room B2. . . . . . . . . . . . . . . 82

H. Pylori: Treatment And Antibiotic Resistance – Room 7.1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84

Diverticular Disease: From Bench To Bedside – Room E2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

Mechanisms Of Carcinogenesis In The Pancreas – Room E3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

Microbiology And Immunology Of The Small Intestine – Room B5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

Abstracts On Fire: Predicting And Optimising IBD Outcome – Hotspot . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94

How To Manage Early Gastric Cancer? – Room F2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98

Malignant Colorectal Polyp: What To Do? – Room A2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

Impacts Of Biologics In IBD – Room B2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

Optimising Your Colonoscopy Practice – Room 7.1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

H. Pylori: From Pathophysiology To The Clinic – Room E2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

Pancreatic Cancer: Risk Factors And Screening – Room E3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107

Carcinogenesis And Tumour Progression In GI Cancer – Room B5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110

Multidisciplinary Management Of Complicated Luminal Crohn’s Disease – Hall 6 . . . . . . . . . . . . . . . . . . . 112

Case Finding And Surveillance Of Barrett’s Oesophagus – Room C1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113

Potential Future Targets In IBD – Room A3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114

Quality Assurance In Colonoscopy: Room For Improvement? – Room B2 . . . . . . . . . . . . . . . . . . . . . . . . . 116

Emerging Biomarkers In GI Cancer Medicine – Room B3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119

Randomised Controlled Trials In Functional Lower GI Disorders – Room 7.1 . . . . . . . . . . . . . . . . . . . . . . 120

Autoimmune And Cholestatic Liver Diseases: Novelties – Room E2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122

From Prevention To Therapy Of Oesophalo-Gastric Cancer – Room E3. . . . . . . . . . . . . . . . . . . . . . . . . . . 125

Nerves & Barrier Function In Health & Disease – Room B5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128

Abstracts On Fire: Hepatobiliary And Pancreatic Malignancies: From Bench To Bedside – Hotspot . . . . . . . 130

viii

Wednesday, November 01, 2017

Pancreato-Biliary Eus: How To Do It Better? – Room A1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134

Submucosal Endoscopy: Indications, Techniques And Outcomes – Room B2 . . . . . . . . . . . . . . . . . . . . . . . 135

Endoscopic Management Of GI Bleeding: What Is New? – Room E4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

Long-Term Complications In IBD – Room 7.1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

Pathogenesis Of IBD – Room E2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141

Can Colonic Polyps Be Diagnosed In Real Time? – Room E3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143

Microbiota In Liver Disease – Room B3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144

Hot Topics In GORD And EOE – Room E4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145

Safety And Long-Term Outcomes With Biologics In IBD – Room 7.1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

Therapeutic Approaches Targeting The Tumour Environment In Pancreatic Cancer: Hope Or Hype? – Room E1151

Endoluminal And Transluminal Interventions In The Upper GI Tract – Room E2 . . . . . . . . . . . . . . . . . . . 152

Bugs In Lower GI Diseases – Room E3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154

Abstracts On Fire: Diagnosis And Treatment Of Upper GI Diseases In Children And Adults – Hotspot . . . . 156

Monday, October 30, 2017

Liver And Biliary I – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161

Pancreas I – Hall 7. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193

Endoscopy And Imaging I – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208

IBD I – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262

Other Lower GI Disorders I – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310

Oesophageal, Gastric And Duodenal Disorders I – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 338

H. Pylori I – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372

Small Intestinal I – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377

Nutrition I – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381

Paediatric: Upper GI – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 388

Tuesday, October 31, 2017

Liver & Biliary II – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393

Paediatric: Liver, Biliary And Pancreas – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423

Pancreas II – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423

Endoscopy And Imaging II – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437

Surgery II – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489

IBD II – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495

Paediatric: Lower GI – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 538

Other Lower GI Disorders II – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 542

Oesophageal, Gastric And Duodenal Disorders II – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 569

ixix

H. Pylori II – Hall 7. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 600

Small Intestinal II – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605

Wednesday, November 01, 2017

Nutrition II – Hall 7. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 616

Liver And Biliary III – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 621

Pancreas III – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 650

Endoscopy And Imaging III – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 664

Surgery III – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 709

IBD III – Hall 7. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 714

Other Lower GI Disorders III – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 755

Oesophageal, Gastric And Duodenal Disorders III – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 781

H. Pylori III – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 814

Small Intestinal III – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 820

Nutrition III – Hall 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 829

Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 837

x

UEG Week 2017 Oral Presentations

MONDAY, OCTOBER 30, 2017 08:00-10:00OPENING SESSION: PART I - HALL 6____________________

OP001 DIAGNOSTIC YIELD OF ‘‘ARTIFICIAL INTELLIGENCE’’-ASSISTED ENDOCYTOSCOPY FOR COLORECTAL POLYPS: APROSPECTIVE STUDY

Y. Mori1, S. Kudo1, M. Misawa1, K. Takeda1, K. Ichimasa1, Y. Ogawa1,Y. Maeda1, T. Kudo1, K. Wakamura1, T. Hayashi1, T. Baba1, F. Ishida1,H. Inoue2, M. Oda3, K. Mori31Digestive Disease Center, Showa University Northern Yokohama Hospital,Yokohama/Japan2Digestive Disease Center, Showa University Koto-Toyosu Hospital, Tokyo/Japan3Graduate School Of Informatics, Nagoya University, Nagoya/Japan

Contact E-mail Address: [email protected]: Computer-aided diagnosis (CAD) powered by artificial intelligenceis attracting increased attention as an option to improve the performance ofoptical biopsy for evaluating colorectal polyps [1]. Although positive preliminarydata have been shown for applying CAD to endocytoscopy (EC) (500-fold ultra-magnifying endoscopy; Olympus Corp., Tokyo, Japan) [2, 3], no prospectivestudies have been reported.Aims & Methods: The present study is an initial prospective trial to validate thefeasibility of applying CAD to endocytoscopy in a routine colonoscopy practice.A total of 88 patients (38 women, 50 men; mean age 64 years) in whom colorectalpolyps had been detected using EC for colonoscopy were prospectively enrolledin the study between January and March 2017. When a polyp was detected, anon-site endoscopist predicted the polyp pathology using the CAD system [2],which was designed to output the predicted pathology of the target lesion—whether neoplastic or non-neoplastic—together with the probability of the diag-nosis (0–100%) immediately after obtaining a methylene blue-stained EC image.The endoscopists obtained as many images as they thought were needed, each ofwhich was evaluated using image-based analysis. The diagnostic ability of theCAD for each image was assessed with reference to the final pathology of theresected specimen. The main outcome measures were diagnostic sensitivity spe-cificity, accuracy, positive predictive value, and negative predictive value of theCAD system for identifying neoplastic change with high confidence (probability�90%). Prior to initiating the trial, 13,861 EC images were used for machine-learning the CAD model.Results: Overall, 126 lesions (62 neoplastic lesions, 64 non-neoplastic lesions;mean size 6mm) were detected, all of which were successfully analyzed usingthe CAD system. A total of 1014 EC images of neoplastic lesions and 1480 ECimages of non-neoplastic lesions were obtained during the colonoscopies of thesepatients. Among them, 55% (1378/2494) were diagnosed with high confidence(CAD probability was �90%). The sensitivity, specificity, accuracy, positivepredictive value, and negative predictive value of the CAD system in identifyingneoplastic change with high confidence were 97%, 67%, 83%, 78%, and 95%,respectively (Table). No complications occurred during the study.

pathologyneoplastic non-neoplastic

Diagnosis of CAD with highconfidence

neoplastic 733 208

non-neoplastic 20 417

Conclusion: This prospective trial revealed that applying CAD to EC was feasi-ble, with a negative predictive value of 490%, which is likely to meet the thresh-old required for optical biopsy of colorectal polyps. Our next goal is to increasethe proportion of high confidence diagnoses, which is currently limited to 55%.(This study is registered as UMIN Clinical Trial Registry No. 000013917 andsupported by Grants-in-Aid for Scientific Research No. 15K19351 from theJapan Society for the Promotion of Science.)Disclosure of Interest: All authors have declared no conflicts of interest.

References

1. Mori Y, Kudo SE, Berzin TM, et al. Computer-aided diagnosis for colono-scopy. Endoscopy, in press

2. Mori Y, Kudo SE, Chiu PW, et al. Impact of an automated system forendocytoscopic diagnosis of small colorectal lesions: an international web-based study. Endoscopy 2016 48: 1110–1118

3. Misawa M, Kudo SE, Mori Y, et al. Characterization of colorectal lesionsusing a computer-aided diagnostic system for narrow-band imaging endocy-toscopy. Gastroenterology 2016 150: 1531–1532

OP002 GENOME-WIDEASSOCIATION STUDY IDENTIFIES INVERSION IN THE CTRB1-CTRB2 LOCUS TO MODIFY RISK FOR ALCOHOLIC AND NON-ALCOHOLIC CHRONIC PANCREATITIS

J. Rosendahl1, H. Kirsten2, E. Hegyi3, P. Kovacs4, F.U. Weiss5, H. Laumen6,P. Lichtner7, C. Ruffert8, J. Chen9, E. Masson9, S. Beer10, C. Zimmer10,K. Seltsam10, A Pan-European Working Group On Alcoholic ChronicPancreatitis (All Names Will Be Displayed At The Conference)11, J. Mössner10,C. Férec9, P. Michl1, J.P. h. Drenth12, H. Witt13, M. Scholz2, M. Sahin-Tóth141Clinic For Internal Medicine I, University Clinic Halle (Saale), Halle (Saale)/Germany2Institute for Medical Informatics, Statistics and Epidemiology, University ofLeipzig, Leipzig, Germany, Leipzig/Germany3Center for Exocrine Disorders, Department of Molecular and Cell Biology, BostonUniversity Henry M. Goldman School of Dental Medicine, Boston, MA 02118,USA, Boston/United States of America4Leipzig University Medical Center, IFB Adiposity Diseases, University of Leipzig,Leipzig, Germany, Leipzig/Germany5Department of Internal Medicine A, Ernst-Moritz-Arndt University, Greifswald,Germany, Greifswald/Germany6Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), PaediatricNutritional Medicine, Technische Universität München (TUM), Freising,Germany, München/Germany7Institute of Human Genetics, Helmholtz Centre Munich, German Research Centrefor Environmental Health, Neuherberg, Germany, München/Germany8Department of Internal Medicine I, Martin Luther University, Halle, Germany,Halle (Saale)/Germany9Institut National de la Santé et de la Recherche Médicale (INSERM), U1078;Etablissement Français du Sang (EFS) – Bretagne; Faculté de Médecine et desSciences de la Santé, Université de Bretagne Occidentale; Laboratoire de GénétiqueMoléculaire et d’Hist, Brest/France10Department of Internal Medicine, Neurology and Dermatology, Division ofGastroenterology, University of Leipzig, Leipzig, Germany, Leipzig/Germany11Universities in Europe, Europe/Germany12Gastroenterology And Hepatology, Radboud University Nijmegen MedicalCentre - Gastroenterology and Hepatology, Radboud University Nij, Nijmegen/Netherlands13Department Of Pediatrics, Technical University Munich, Munich/Germany14Boston University, Boston/United States of America

Contact E-mail Address: [email protected]: Alcohol-related pancreatitis is associated with a disproportionatelylarge number of hospitalizations among gastrointestinal disorders. Despite itsclinical importance, genetic susceptibility to alcoholic pancreatitis is poorly char-acterized. Our aim was to identify risk genes for alcoholic chronic pancreatitis(CP) and to evaluate their relevance in non-alcoholic CP. Therefore, we per-formed a genome-wide association study and functional characterization of anew pancreatitis locus.Aims & Methods: Patients with CP were collected according to a standardizedprotocol throughout Europe. DNA extracted from peripheral blood samples wasused for genetic investigations with Illumina technology, PCR, and melting curveassays. In total, 1959 European alcoholic CP patients and population-basedcontrols from the KORA, LIFE and INCIPE study (n¼ 4708) as well as chronicalcoholics from the GESGA consortium (n¼ 1332) were investigated.Replication was performed in three European cohorts comprising 1650 patientswith non-alcoholic CP and 6695 controls originating from the same countries.Results: We replicated previously reported risk loci PRSS1-PRSS2, CLDN2-MORC4, SPINK1 and CTRC in alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a new risk locus with lead SNP rs8055167(odds ratio, 1.35 [95% CI 1.23 to 1.6]; P¼ 4.2� 10�9). We found that a 16.6 kbinversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and best tagged by rs8048956. The association was also success-fully replicated in three independent European non-alcoholic CP cohorts of 1,650 patients and 6695 controls (odds ratio, 1.62 [95% CI 1.42 to 1.86];P¼ 1.64� 10�12). The inversion changes the expression ratio of CTRB1 andCTRB2 isoforms and thereby affects protective trypsinogen degradation andultimately pancreatitis risk.Conclusion: Our GWAS identified CTRB1-CTRB2 as a new risk locus for ACPand NACP. The association within the CTRB1-CTRB2 locus was linked to a16.6 kb inversion that altered CTRB1/CTRB2 expression thereby affecting pro-tective trypsinogen degradation. Furthermore, we confirmed association of ACPwith the PRSS1-PRSS2, CLDN2-MORC4, CTRC and SPINK1 loci. Takentogether, the identified risk variants explained about 18% of the variance inACP. Our discovery provides strong evidence for common pathogenic mechan-isms underlying the complex etiology of ACP and NACP.Disclosure of Interest: All authors have declared no conflicts of interest.


2017, Vol. 5(5S) A1–A160

! Author(s) 2017



DOI: 10.1177/2050640617725668


MONDAY, OCTOBER 30, 2017 10:30-12:00OPENING SESSION: PART II - HALL 6____________________

OP003 DIFFERENTIALLY O-GLYCOSYLATED CARBOXYL ESTERLIPASE CAUSES A MODY8-LIKE PHENOTYPE IN MICE

B. Mercanoglu, G. Wolters-Eisfeld, C. Güngör, J.R. Izbicki, M. BockhornDepartment Of General, Visceral And Thoracic Surgery, University MedicalCenter Hamburg-Eppendorf, Hamburg/Germany

Contact E-mail Address: [email protected]: Maturity-onset diabetes of the young type 8 (MODY8) is a mono-genic syndrome of diabetes and a pancreatic exocrine dysfunction caused bymutations in exon 11 of the Carboxyl Ester Lipase (CEL) gene where clusteredO-GalNAc glycosylation sites are encoded.1 C-terminal truncated CEL reducesthe viability of pancreatic acinar and beta cell models, indicating the induction ofapoptosis in pancreatic cells.2

Aims & Methods: The aim of the present study was to establish a mouse modelthat might allow for the investigation of the pathophysiological mechanisms inMODY8. Therefore, we hypothesized that truncated O-glycosylation of Cel (Cel-Tn) is responsible for the MODY8 phenotype and investigated the pathogenicityof differentially glycosylated Cel. For this purpose, we generated a transgenicmouse model with a conditional Cosmc knockout mediated by the pancreasspecific transcription factor 1a (Ptf1a)-cre mouse strain to induce Tn antigenexpression in pancreatic acinar cells and thereby truncated O-glycan formation.Results: In accordance with the reported cluster of symptoms inMODY8 patients,characterization of Cosmc-deficient mice revealed symptoms of exocrine pancrea-tic insufficiency with maldigestion, altered stool formation, impaired zymogengranule release and decreased enzymatic elastase and lipase activity. Moreover,examination of fasting serum glucose and HbA1c displayed elevated levels andreduced amount of fasting serum C-peptide conformable with diabetes based onbeta-cell failure. Furthermore, we observed reduced numbers of pancreatic islets inCosmc knockout mice indicating cytotoxicity of Cel-Tn. Our results indicate thatthe impairment of O-glycosylation on Cel was responsible for the observedMODY8-related phenotype, similar to mutation induced C-terminal truncation.Conclusion: In summary, this study demonstrates that deletion of Cosmc in pan-creatic acinar cells leads to the loss of O-glycosylation, with consecutive expres-sion of Tn-modified Cel, thus resulting in a MODY8 phenotype. These findingsdemonstrate the first generation of a MODY8-like phenotype in a mouse modeland implicate the relevance of O-glycan formation.Disclosure of Interest: All authors have declared no conflicts of interest.

References

1. Raeder, H., Johansson, S., Holm, P.I., Haldorsen, I.S., Mas, E., Sbarra, V.,Nermoen, I., Eide, S.A., Grevle, L., Bjorkhaug, L., et al. (2006). Mutationsin the CEL VNTR cause a syndrome of diabetes and pancreatic exocrinedysfunction. Nat Genet 38, 54–62.

2. Torsvik, J., Johansson, B.B., Dalva, M., Marie, M., Fjeld, K., Johansson, S.,Bjorkoy, G., Saraste, J., Njolstad, P.R., and Molven, A. (2014). Endocytosisof secreted carboxyl ester lipase in a syndrome of diabetes and pancreaticexocrine dysfunction. J Biol Chem 289, 29097–29111.

OP004 BENEFITS OF H. PYLORI ERADICATION IN PREVENTINGGASTRIC CANCER IN THE OLDER POPULATION: RESULTS FROMA POPULATION-BASED STUDY

W.K. Leung1, I. O. Wong2, E.W. Chan3, A.Y. Wong3, K.F. Yeung2, L. Chen4,I.C. Wong5, K.S. Cheung11Department Of Medicine, University of Hong Kong, Hong Kong/Hong Kong PRC2School Of Public Health, University of Hong Kong, Hong Kong/Hong Kong PRC3Department Of Pharmacology And Pharmacy, The University of Hong Kong,Queen Mary Hospital, Hong Kong, Hong Kong/Hong Kong PRC4Department Of Medicine, The University of Hong Kong, Hong Kong/Hong KongPRC5UCL School Of Pharmacy, University College London, London/United Kingdom

Contact E-mail Address: [email protected]: Although H. pylori (HP) eradication has been shown to reduce therisk of gastric cancer development, it remains elusive whether there is a point ofno return on the HP-associated gastric carcinogenesis cascade. In particular,there are limited data on the benefits of HP eradication on gastric cancer pre-vention in the older population (�60 years).Aims & Methods: We aimed to compare the age-specific risk of gastric cancerdevelopment in a large cohort of HP infected subjects who had received HPeradication therapy with the local general population.Methods: The results were based on a retrospective cohort study that included allHP-infected subjects who had received a �7-day course of clarithromycin-basedtriple therapy between 2003 and 2012 in Hong Kong. These subjects were iden-tified from a territory-wide health database, which captured all patients’ clinicalinformation in the local public health care system. We excluded subjects withhistory of gastrectomy, were diagnosed to have gastric cancer prior to or within12-month of HP therapy, and those who failed clarithromycin-based triple ther-apy. Person-years at risk were derived for each patient from the first date of HPtherapy until the date of gastric cancer diagnosis, death or the date of censoring.Expected number of gastric cancer cases in the general population were estimatedon data from the population-based Hong Kong Cancer Registry. We determinedthe standardized incidence ratio (SIR) of the HP eradicated cohort and the

general population of the same age group which included both HP-infectedand non-infected subjects. All analyses were conducted by a priori age groupsof 540, 40–59.9 and �60 years.Results: Among the 63,397 eligible HP-infected subjects (median age 54.0 years,46.5% male) who had received clarithromycin-based triple therapy, 153 (0.2%)developed gastric cancer with a median follow-up of 7.4 years (overall incidence:3.2 per 10,000 person-years). The cumulative gastric cancer incidence rates in theHP-eradicated cohort at 12 years were 0.1%, 0.3% and 0.8% for the540, 40–59.9and �60 years groups, as compared to 0.1%, 0.3% and 1.1% for the estimatedcumulative incidence rates in the matched age groups of the general population.Among the �60 years group, the risk of gastric cancer was significantly lower inthe HP eradicated group as compared to the general population (SIR¼ 0.75; 95%CI, 0.61 to 0.92), corresponding to a 25% reduction in gastric cancer incidence.In contrast, the corresponding SIRwas 1.37 (95%CI, 0.43 – 3.30) in the540 yearsand 1.07 (95% CI, 0.82 – 1.38) in the 40–59.9 years groups.Conclusion: In this large population-based study of HP-eradicated subjects, wefound that the risk of gastric cancer was significantly lower among those whoreceived HP eradication at �60 years than the age-matched general population.Our results suggest benefits of HP eradication on gastric cancer prevention evenin the aged population.Disclosure of Interest: All authors have declared no conflicts of interest.

MONDAY, OCTOBER 30, 2017 10:30-12:00CLINICAL TRIALS IN CROHN’S DISEASE -ROOM F3____________________

OP005 EFFECT OF DISEASE DURATION AND LOCATION ONCLINICAL REMISSION IN CROHN’S DISEASE PATIENTS TREATEDWITH FILGOTINIB, A SELECTIVE JAK1 INHIBITOR: POST-HOCANALYSIS FROM THE PHASE 2 FITZROY STUDY

S. Vermeire1, A. Van Der Aa2, C. Jamoul2, C. Tasset2, P. Harrison2, G.R. D’Haens31Department of Gastroenterology, University Hospitals Leuven, Leuven/Belgium2Galapagos NV, Mechelen/Belgium3Gastroenterology, Academic Medical Centre, Amsterdam/Netherlands

Contact E-mail Address: [email protected]: Filgotinib is an oral, selective Janus kinase 1 (JAK1) inhibitor, withdemonstrated efficacy in rheumatoid arthritis. This 20-week Phase 2 study eval-uated the efficacy and safety of filgotinib in patients with active Crohn’s disease(CD). The primary endpoint (CDAI remission at Week 10) was met with anacceptable safety profile1.Aims & Methods: The effect of disease duration and location has been assessedpost-hoc on the primary endpoint. 174 patients with moderate-to-severely activeCD (CDAI: 220 to 450) and ulcerations confirmed by centrally read endoscopywere randomized 3:1 to receive 200mg filgotinib (FIL) or placebo (PBO) QD for10 weeks. Immunosuppressants were discontinued prior to treatment initiationbut corticosteroid-treated patients remained stable until Week 10 (W10). Patientsnaı̈ve to anti-TNF therapy as well as patients previously exposed to anti-TNFwith no response or loss-of-response were included. Clinical remission at W10was analysed by disease duration (55 years (yrs), 5–10 yrs and 410 yrs) andhistorical location (ileal, ileo-colonic, colonic).Results: Baseline disease characteristics were similar in both initial treatmentgroups, showing a population of active Crohn’s patients (mean CDAI 293, meanSES-CD 14.6, mean CRP 15.6mg/L, 41% 410mg/L, oral corticosteroids use51%, mean daily dose 21.6mg). Forty-two percent of patients were anti-TNFnaı̈ve, 58% were anti-TNF non-responder. Forty-three percent were diagnosedfor less than 5 yrs, 30% between 5 and 10 yrs and 27% for 410 yrs. Most anti-TNFnaı̈ve patients (63%) had55 yrs CD, whereas 71%of anti-TNF non-respon-ders were diagnosed 45 yrs. A total of 62% of patients had ileo-colonic disease,whereas 18% had ileal involvement only and 20% had only colonic involvement.The percentage of FIL-treated patients in clinical remission atW10 is not impactedby longer disease duration while for PBO-treated patients the percentage of remit-ters was lower with disease duration of 410 yrs. In FIL-treated patients, consis-tently high remission rates in both anti-TNFnaı̈ve and (to a lesser extent) anti-TNFnon-responders were seen, independently of disease duration (anti-TNF naı̈ve:59%, 60%, 62%; anti-TNF non-responders: 42%, 37%, 32%, for respectively55 yrs, 5–10 yrs and410 yrs). FIL treatment effect was also shown independentof disease location, although a higher percentage of remitters was observed in thesubgroup with colonic disease only (Table 1).

Table 1: CDAI remission at Week 10 by subgroup

Subgroup population filgotinib n¼ 128 placebo n¼ 44

Disease duration

55 years 28/53 (53%) 5/21 (24%)5–10 years 17/40 (43%) 3/11 (27%)

410 years 15/35 (43%) 2/12 (17%)Disease location

ileal 10/24 (42%) 1/7 (14%)

Ileo-colonic 31/76 (41%) 8/31 (26%)

colonic 19/28 (68%) 1/6 (17%)

CDAI: Crohn’s Disease Activity Index

A2 United European Gastroenterology Journal 5(5S)

Conclusion: This post-hoc analysis of the Phase 2 FITZROY study indicates thatinhibition of JAK1 with filgotinib in Crohn’s patients is consistently associatedwith clinical remission, independently of disease duration and location.Disclosure of Interest: S. Vermeire: � Grant support: AbbVie, MSD, Takeda �Lectures: AbbVie, Falk Pharma, Ferring, Hospira, MSD, Takeda, Tillotts �Consultancy: AbbVie, Celgene, Ferring, Galapagos, Genentech/Roche,Hospira, J&J, MSD, Mundipharma, Pfizer, Second Genome, Shire, TakedaA. Van der Aa: employee of Galapagos NVC. Jamoul: consultant for Galapagos NVC. Tasset: employee of Galapagos NVP. Harrison: employee of Galapagos NVG.R. D’Haens: Abbvie, Ablynx, Biogen, BMS, BoehringerIng., Celgene,Celltrion, Ferring, Galapagos, Gilead, GSK, Hospira, Immunic, J&J, Lycera,Millen./Takeda, MitsubishiPh., MSD, Mundiph., NovoNordisk, Pfizer,Protagonist, Robarts, Salix, Sandoz, Shire, Teva, Tigenix, Tillotts, a.o.

Reference

1. Vermeire S., et al. Lancet. 2016; 389(10066):266–275

OP006 EXPOSURE-RESPONSE TO SC USTEKINUMAB INMODERATE – SEVERE CROHN’S DISEASE: RESULTS FROM THEIM-UNITI MAINTENANCE STUDY

O. J. Adedokun1, Z. Xu1, C. Gasink1, D. Jacobstein1, P. Szapary1, J. Johanns1,L. Gao1, H. M. Davis1, S. Hanauer2, B.G. Feagan3, S. Ghosh4, W. Sandborn51JanssenResearch&Development,LLC,SpringHouse/UnitedStatesofAmerica/PA2Northwestern University Feinberg School of Medicine, Chicago/United States ofAmerica/IL3Robarts Clinical Trials Inc., Robarts Research Institute, Western University,London/Canada4Institute of Translational Medicine, Birmingham/United Kingdom5University of California San Diego, La Jolla/United States of America/CA

Contact E-mail Address: [email protected]: Subcutaneous (SC) Ustekinumab (UST) maintenance was pre-viously shown to maintain clinical response and remission in mod-severeCrohn’s disease (CD) in the Phase 3 IM-UNITI maintenance trial, but detailedexposure-response analyses using clinical efficacy, biomarkers of inflammation,and endoscopic substudy data have not yet been presented.Aims & Methods: Patients achieving clinical response after a single IV dose ofUST in the UNITI-1&2 induction studies were randomized 1:1:1 in IM-UNITIto SC placebo (PBO), UST 90mg q12w, or q8w. Ustekinumab concentrationdata were categorized into quartiles (Q) and ER relationships were assessedbased on wk24 steady-state (ss) trough or average ss trough values vs clinicalremission, CRP, and endoscopic remission and response (SES-CD5 2 or 50%decrease, respectively) in endoscopic substudy patients. The association betweenss trough and efficacy outcomes was assessed using a one-sided CochraneArmitage trend test. Optimal concentration cut-offs for remission were evaluatedusing ROC analysis.Results: Median ss troughs were approximately 3x greater with q8w SC UST(2.11mg/mL and 0.62mg/mL for the q8w and q12w regimen respectively). USTlevels were lower in patients with higher baseline CRP (likely reflecting greaterinflammatory burden), while oral AZA, 6-MP, or MTX use and weight did nothave any notable effect. Both q8w and q12w were associated with higher propor-tions achieving clinical remission (eg4 0.92 mg/ml in q8w Qs), lower CRP con-centrations (in Qs4 1.05mg/ml), and endoscopic response and remission (inQs4 0.5 mg/ml) compared to PBO (Table). By ROC analyses, trough concentra-tions between 0.8 and 1.4 mg/mL or greater were associated with greater main-tenance of clinical remission.

Efficacy OutcomeMain Study (Week 24 trough concentration)

Q1 Q2 Q3 Q4 p-value*N¼ 47 N¼ 48 N¼ 48 N¼ 48

Remission at Week 24 55.3% 70.8% 77.1% 81.3% 0.002

CRP normalizationat Week 24

23.4% 27.1% 47.9% 56.3% 50.001

Endoscopy Substudy (Average trough concentration)N¼ 25 N¼ 25 N¼ 25 N¼ 25

Endoscopic responseat Week 44

7.7% 40.0% 34.6% 44.0% 0.006

Endoscopic remissionat Week 44

7.7% 24.0% 19.2% 28.0% 0.054

Main Study: Q1: �0.5 mg/mL, Q2: 40.5 to �1.1 mg/mL, Q3: 41.1 mg/mL to�2.5 mg/mL, 42.5mg/mL Endoscopic Substudy: Q1: �0.5 mg/mL, Q2: 40.5 to�1.4 mg/mL, Q3: 41.4 mg/mL to �2.7 mg/mL, 42.7 mg/mL *p-values for a one-sided Cochrane Armitage trend test for the proportions of subjects achievingoutcomes across ustekinumab concentration quartiles

Conclusion: In Crohn’s disease patients in the IM-UNITI maintenance study,ustekinumab concentrations were positively associated with clinical efficacy out-comes and inversely related to CRP concentrations.Disclosure of Interest: O.J. Adedokun: Janssen Scientific Affairs, LLC employeeZ. Xu: Janssen Scientific Affairs, LLC employeeC. Gasink: Janssen Scientific Affairs, LLC employeeD. Jacobstein: Janssen Scientific Affairs, LLC employeeP. Szapary: Janssen Scientific Affairs, LLC employeeJ. Johanns: Janssen Scientific Affairs, LLC employeeL. Gao: Janssen Scientific Affairs, LLC employeeH.M. Davis: Janssen Scientific Affairs, LLC employeeS. Hanauer: Investigator for Janssen Research & Development, LLCB.G. Feagan: Janssen Scientific Affairs, LLC investigatorS. Ghosh: Investigator for Janssen Research & Development, LLCW. Sandborn: Investigator for Janssen Research & Development, LLC

OP007 SAFETY AND EFFICACY OF UPADACITINIB (ABT-494), ANORAL JAK1 INHIBITOR, AS INDUCTION THERAPY IN PATIENTSWITH CROHN’S DISEASE: RESULTS FROM CELEST

W. J. Sanborn1, B. Feagan2, J. Panes3, G. D’Haens4, J. Colombel5, Q. Zhou6,B. Huang6, J.V. Enejosa6, A. L. Pangan6, A. P. Lacerda61University of California San Diego, La Jolla/United States of America/CA2Robarts Clinical Trials, Western University, London/Canada/ON3Hospital Clı́nic Barcelona, Department of Gastroenterology, Baecelona/Spain4Academic Medical Centre, Amsterdam/Netherlands5Icahn School of Medicine at Mount Sinai, New York/United States of America6AbbVie Inc., North Chicago/United States of America

Contact E-mail Address: [email protected]: The efficacy and safety of upadacitinib (UPA), an oral JAK1 inhi-bitor, were assessed in patients with moderate-to-severe Crohn’s disease (CD)who had inadequate response/intolerance to an immunomodulator or tumornecrosis factor (TNF) antagonist.Aims & Methods: Adult patients with active CD, with a CDAI 220–450, anaverage daily liquid/soft stool frequency (SF) �2.5 or daily abdominal pain(AP) score �2.0, and Simplified Endoscopic Score for CD (SES-CD) �6 (or�4 for those with isolated ileal disease), were randomized 1:1:1:1:1:1 todouble-blind induction therapy with placebo (PBO) or UPA at 3, 6, 12, 24mgtwice daily (BID) or 24mg once daily (QD) for 16 weeks, followed by blindedextension therapy for 36 weeks. Patients were also randomized 1:1 at baseline forfollow-up ileocolonoscopy at either Week 12/16. From Week 2, steroid doseswere to be tapered in patients on corticosteroids at baseline. Co-primary end-points were clinical remission (SF� 1.5 and AP� 1, and both not worse thanbaseline) at Week 16, and endoscopic remission (SES-CD �4 and �2 pointreduction from baseline, no subscore 41) at Week 12/16. Secondary endpointsincluded clinical response (�30% reduction from baseline in AP or SF withneither worse than baseline), and endoscopic response (�25% decrease in SES-CD). The overall dose-response relationship between multiple UPA doses andPBO was tested by Multiple Comparison Procedures Modeling (MCP-Mod);pairwise comparison between each UPA dose with PBO was tested byCochran-Mantel-Haenszel test stratified by baseline SES-CD.Results:Of the 220 enrolled patients, 180 (82%) completed 16 weeks of induction.Mean age was 40.7� 12.9 yrs, CDAI 302.7� 63.4 and disease duration13.2� 10.0 yrs. Ninety six percent had failed, or were intolerant to TNF antago-nists. Significantly more patients on 6mg BID achieved clinical remission. Asignificant dose-response relationship was observed with UPA vs PBO for endo-scopic remission (Table 1). Compared with PBO, more patients achieved clinicalresponse with 6 and 24mg BID, and endoscopic response with UPA doses �6mgBID at Week 16 (Table 1). Adverse events (AEs) and infections were numericallyhigher with UPA. Serious AEs and discontinuations were similar in all groups,except for 12mg BID. One case each of non-melanoma skin cancer and herpeszoster were reported in the 24mg BID group, two gastrointestinal perforationswere reported, one each in the 24mg BID and 24mg QD groups). Two adjudi-cated cardiovascular events (myocardial infarction) were reported in the 12mgBID group. One death was reported during screening; the patient did not receivestudy drug. Laboratory abnormalities were mostly �Grade 2, with 3 events ofGrade 3 hemoglobin decrease (0 on PBO) and 5 Grade 3 CPK elevations (1 onPBO/ 4 on UPA).Conclusion: This dose-ranging study demonstrated endoscopic improvement andclinical benefit of upadacitinib at doses of 6mg BID and higher as inductiontherapy in patients with moderate-to-severe refractory CD, and a safety profile asexpected with a JAK inhibitor in this population.Disclosure of Interest: W.J. Sanborn: Consultant for AbbVie, ActoGeniX NV,AGI Therapeutics, Inc., Alba Therapeutics Corporation, and others. Receivedspeakers fees from AbbVie, Bristol-Myers Squibb, and Janssen; financial supportfor research from AbbVie, Bristol-Myers Squibb and others.B. Feagan: Consultant/advisory board member for AbbVie, Allergan,ActoGeniX, Albireo, Amgen, and others; received speaker’s fees from AbbVie,JnJ/Janssen; and financial support for research from AbbVie Inc., Amgen Inc.,AstraZeneca/MedImmune Ltd., and others.J. Panes: Consultant or advisory member for AbbVie, Arena Pharmaceuticals,Boehringer Ingelheim, BMS, and others; speaker for AbbVie, Ferring, Janssen,

United European Gastroenterology Journal 5(5S) A3

MSD, Shire Pharmaceuticals and Tillots; received research funding from AbbVieand MSD;G. D’Haens: Consulting/lecture fees from AbbVie, ActoGeniX, AIM,Boehringer Ingelheim GmbH, Centocor, Chemo Centryx, and others; researchgrants from AbbVie, Janssen, Given Imaging, and others; speaking honorariafrom AbbVie, Tillotts, and others.J. Colombel: Consultant or advisory board: AbbVie, Amgen, Boehringer-Ingelheim, and others. Speaker: AbbVie, Ferring. Speaker’s bureau: Amgen.Stock options: Intestinal Biotech Development, Genefit. Research Grants:AbbVie, Takeda, Janssen and Janssen.Q. Zhou: Employee of AbbVie Inc. and may own stock and/or options.B. Huang: Employee of AbbVie Inc. and may own stock and/or options.J.V. Enejosa: Employee of AbbVie Inc. and may own stock and/or options.A.L. Pangan: Employee of AbbVie Inc. and may own stock and/or options.A.P. Lacerda: Employee of AbbVie Inc. and may own stock and/or options.

OP008 EFFICACY AND SAFETY OF OPEN-LABEL MAINTENANCETHERAPY WITH SUBCUTANEOUS RISANKIZUMAB IN PATIENTSWITH MODERATE-TO-SEVERE CROHN’S DISEASE

B. G. Feagan1, J. Panés2, M. Ferrante3, A. Kaser4, G. R. D’Haens5,W.J. Sandborn6, E. Louis7, M.F. Neurath8, D. Franchimont9, O. Dewit10,U. Seidler11, K. Kim12, C. Selinger13, S. J. Padula14, I. Herichova15, A.M. Robinson16, K. Wallace16, J. Zhao16, A. Soaita17, S. Visvanathan17,D. Hall17, W. O. Böcher141Robarts Clinical Trials, London/Canada2Hospital Clinic Barcelona, Barcelona/Spain3University Hospitals Leuven, Leuven/Belgium4University of Cambridge, Addenbrooke’s Hospital, Cambridge/United Kingdom5Academic Medical Center, University of Amsterdam, Amsterdam/Netherlands6IBD Center University of California San Diego and UC San Diego HealthSystem, San Diego/United States of America/CA7University Hospital CHU Liège, Liège/Belgium8University of Erlangen, Erlangen/Germany9Erasme University Hospital, Brussels/Belgium10Cliniques Universitaires Saint-Luc, Brussels/Belgium11Hannover Medical School, Hannover/Germany12Asan Medical Center, Seoul/Korea, Republic of13St James University Hospital, Leeds/United Kingdom14Boehringer Ingelheim Pharma Gmbh & Co. KG, Ingelheim/Germany15Boehringer Ingelheim RCV GmbH & Co KG, Vienna/Austria16AbbVie Inc., North Chicago/United States of America17Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield/United States ofAmerica/CT

Contact E-mail Address: [email protected]: The IL-23 pathway is implicated in the pathogenesis of Crohn’sdisease (CD) both genetically and biologically.Aims & Methods: The efficacy and safety of risankizumab (RZB), a humanisedmonoclonal antibody that inhibits IL-23 through specific targeting of the IL-23p19 subunit, was assessed in a randomised Phase II study in patients with mod-erate-to-severe active CD (NCT02031276). The study included a 12-week (wk)double-blind intravenous (iv) induction period (P1), a 14-wk open-label (OL) ivre-induction (600mg RZB)/wash out period (P2) and a 26-wk OL subcutaneous(sc) 180mg RZB maintenance period (P3). RZB was more effective than placebo

for inducing clinical and endoscopic remission at 12 wks. Re-induction therapywith 600mg RZB increased clinical remission rates further at Wk 26, and waswell tolerated over 26 wks. Here, the efficacy and safety of OL sc maintenancetherapy with RZB is reported. Non-responder imputation was used for missingdata.Results: At Wk 26, 62/121 patients were in clinical remission and entered RZBmaintenance treatment, with 54 patients completing treatment to Wk 52. At Wk52, 71.0% of patients (44/62) had clinical remission (Table) and 80.6% (50/62)had clinical response. Of those patients who entered P3 and had clinical remissionat Wk 12, 87.5% (21/24) were still in clinical remission at Wk 52. The rate ofendoscopic response and remission at Wk 52 was 54.8% (34/62) and 35.5% (22/62), respectively. Of those patients who entered P3 and had endoscopic remissionat Wk 12, 69.2% (9/13) were still in endoscopic remission at Wk 52. Overall,29.0% of patients (18/62) were in deep remission at Wk 52. During P3, twopatients discontinued due to an AE (worsening and exacerbation of CD).

Table: Clinical remission at Week 52 by outcome of Period 1 (Week 12) andPeriod 2 (Week 26) for patients who entered Period 3

Original Period 1 treatment designation

TotalPlacebo

Risankizumab

200 mg 600 mg

Pts in clinical remissionat Week 26, N

19 22 21 62

Pts in clinical remissionat Week 52, n (%)

15 (78.9) 13 (59.1) 16 (76.2) 44 (71.0)

Pts in clinical remissionat Weeks 12 and 26,N

5 5 14 24

Pts in clinical remissionat Week 52, n (%)

4 (80.0) 5 (100) 12 (85.7) 21 (87.5)

The proportion of patients in clinical remission at Week 52 after open-labelintravenous re-induction therapy (600mg risankizumab at Weeks 14, 18 and22) or wash out in Period 2 and open-label subcutaneous maintenance therapy(180mg risankizumab) in Period 3 are shown by original Period 1 treatmentdesignation. All patients who were not in deep remission (clinical remission[CDAI 5150] þ endoscopic remission [CDEIS �4; CDEIS �2 for patientswith initial isolated ileitis]) at Week 12 underwent risankizumab re-inductiontherapy in Period 2. Non-responder imputation was used for missing data.CDAI, Crohn’s Disease Activity Index; CDEIS, Crohn’s Disease EndoscopicIndex of Severity

Conclusion: In patients in clinical remission at Wk 26, OL sc RZB was effective inmaintaining clinical and endoscopic remission and response up to Wk 52. Earlyachievement of clinical or endoscopic remission at Wk 12 was associated withbetter outcome at Wk 52. Overall, RZB was well tolerated with no new safetysignals detected during sc maintenance treatment.Disclosure of Interest: B.G. Feagan: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen Biotech/Centocor, Johnson & Johnson/Janssen, Pfizer,Receptos, Takeda, ActoGeniX, Akros, Albireo Pharma, Allergan, AvaxiaBiologics Inc., Avir Pharma, Axcan Pharma, Baxter Healthcare Corporation

Abstract No: OP007Table 1: Efficacy Endpoints at Week 16#f

Endpoints, n (%)PBON¼ 37

3mg BIDN¼ 39

6mg BIDN¼ 37

12mg BIDN¼ 36

24mg BIDN¼ 36

24mg QDN¼ 35

Clinical Remission 4 (11) 5 (13) 10 (27)* 4 (11) 8 (22) 5 (14)

Endoscopic Remission 0 (0.0) 4 (10)* 3 (8) 3 (8)* 8 (22)*** 5 (14)**

Clinical Responsey 12 (32) 17 (44) 21 (57)** 17 (47) 22 (61)** 17 (49)

Modified Clinical Remissionzx 4 (12) 6 (16) 10 (30)* 9 (27) 11 (37)** 6 (19)

Endoscopic Response� 5 (14) 9 (23) 16 (43)*** 14 (39)*** 18 (50)*** 17 (49)***

Endoscopic Improvement�x 1 (3) 5 (13) 7 (21)** 10 (29)*** 10 (33)*** 8 (25)**

CDAI5 150 6 (16) 8 (21) 11 (30) 14 (39)** 11 (31) 7 (20)CR100 10 (27) 13 (33) 15 (41) 16 (44) 20 (56)** 11 (31)

CR70 13 (35) 18 (46) 20 (54) 16 (44) 23 (64)** 17 (49)

Change in hsCRP, Mean (SD) �0.1(12.0) �3.0 (19.6) �3.9 (19.5) �6.6 (27.1) �14.8 (26.4)*** �2.7 (13.7)

CDAI5 150, Crohn’s disease activity index 5150; CR70 or 100, reduction from baseline in CDAI score of 70 or 100 points.Co-primary endpoints are in bold text.fFor endoscopic remission, response and improvement, measurements were at Week 12/16, as scored by the central reader.yClinical response: �30% reduction from baseline in AP or SF, with neither worse than baseline.zModified Clinical remission: average daily SF� 2.8 and average daily AP� 1.0 with both not worse than baseline.�Endoscopic response: �25% decrease in SES-CD from baseline.�Endoscopic improvement: 450% decrease in SES-CD from baseline or endoscopic remission.xIncludes patients with baseline SF� 4 or AP� 2. For PBO, 3, 6, 12, 24mg BID and 24mg QD, N¼ 33, 38, 33, 34, 30 and 32, respectively.#Non-responder imputation.*, ** and ***: statistically significant at .1, .05, and .01 levels, respectively.

A4 United European Gastroenterology Journal 5(5S)

J. Panés: AbbVie, Arena, Boehringer Ingelheim, Galapagos, Genentech/Roche,Janssen, MSD, Pfizer, Takeda, TiGenix and TopiVert.M. Ferrante: Boehringer Ingelheim, Takeda, AbbVie, Falk, Ferring, Janssen,MSD, Tillotts, Chiesi, Mitsubishi Tanabe and Zeria Pharmaceutical Co.A. Kaser: Boehringer Ingelheim, Ferring, Genentech, GlaxoSmithKline,Hospira, Janssen, Kymab, Second Genome and VHsquared Ltd.G.R. D’Haens: AbbVie, Ablynx, Amakem, AM Pharma, Avaxia, Biogen,Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmo,Covidien, enGene, Ferring, Dr FALK Pharma, Galapagos, Gilead,GlaxoSmithKlineW.J. Sandborn: Boehringer Ingelheim, AbbVie, Amgen, Janssen, Lilly andAstraZeneca/MedImmune.E. Louis: AbbVie, MSD, Ferring, Takeda, Celltrion, Mundipharma, Hospiraand Janssen.M.F. Neurath: AbbVie Deutschland GmbH & Co. KG, Bionorica SE,Boehringer Ingelheim GmbH & Co. KG, e.Bavarian Health GmbH, FalkFoundation, F. Hoffmann La Roche GmbH, Genentech Inc., Hexal AG,Index Pharmaceuticals AB, Janssen-Cilag GmbH, MSD Sharp and DohmeGmbH,D. Franchimont: AbbVie, MSD, Amgen, Ferring, Takeda, Mundipharma,Hospira and Pfizer.O. Dewit: AbbVie, MSD, Ferring, Takeda, Mundipharma and Hospira.U. Seidler: Boehringer Ingelheim, Pfizer, Janssen, Roche, Gilead, Salix,Mitsubishi, MSD and Takeda.C. Selinger: Warner Chilcott, AbbVie, Dr Falk, Takeda, Janssen and MSDS.J. Padula: Employee of Boehringer Ingelheim.I. Herichova: Employee of Boehringer Ingelheim.A.M. Robinson: Employee of AbbVie.K. Wallace: Employee of AbbVie.J. Zhao: Employee of AbbVie.A. Soaita: Employee of Boehringer Ingelheim.S. Visvanathan: Employee of Boehringer Ingelheim.D. Hall: Employee of Boehringer Ingelheim.W.O. Böcher: Employee of Boehringer Ingelheim.All other authors have declared no conflicts of interest.

OP009 ENDOSCOPIC AND CLINICAL EFFICACYDEMONSTRATED WITH ORAL OZANIMOD IN MODERATELY TOSEVERELY ACTIVE CROHN’S DISEASE

B. G. Feagan1, W. J. Sandborn2, G. D’Haens3, B. G. Levesque1, B. E. Skolnick4,C. Li4, D. Penenberg4, R. Aranda4, A. Olson41Robarts Research Institute, London/Canada/ON2Division Of Gastroenterology, University of California, La Jolla, San Diego/United States of America/CA3Academic Medical Center, Amsterdam/Netherlands4Receptos, a wholly owned subsidiary of Celgene, San Diego/United States ofAmerica/CA

Contact E-mail Address: [email protected]: Ozanimod, an oral, once-daily immunomodulator designed to selec-tively target S1P1R and S1P5R, has demonstrated clinical efficacy in ulcerativecolitis (UC) (Sandborn NEJM 2016) and is being evaluated in active Crohn’sDisease (CD). This Phase 2 open-label study in CD examined endoscopic andclinical outcomes following treatment with ozanimod 1mg daily for 12 weeks.Aims & Methods: Patients with active CD (Crohn’s Disease Activity Index[CDAI] score 220–450, total simple endoscopic score for CD [SES-CD] �6 (orin isolated ileum disease SES-CD �4) were dosed with ozanimod 1mg daily. Allendoscopic assessments were read in a blinded manner by an imaging core lab.Daily electronic diary records were used to collect CD symptoms (includingabdominal pain and soft/loose stool frequency). SES-CD was evaluated at base-line and Week 12, and CDAI was assessed at baseline and Weeks 4, 8, and 12.Results: Sixty-nine patients were enrolled. At baseline, mean age was 37.7 years,mean SES-CD was 13.3, and mean CDAI was 320. Mean CD duration was 10.0years, with 54% of patients having had prior exposure to biologic therapy (i.e.,TNF-�, vedolizumab). Patients with available data at baseline and Week 12 wereincluded in the analyses, including SES-CD matched endoscopic segments(n¼ 60) and CDAI (n¼ 59). SES-CD score reductions of �25% and �50%from baseline was seen in 43.3% and 26.7% of patients respectively. Patientswith less endoscopic disease activity (baseline SES-CD �12) had a greater endo-scopic response with 50.0% of patients and 35.7% having a reduction of �25%and �50% respectively. In line with the improvements in SES-CD, reductions inmean CDAI scores from baseline were seen as early as Week 4 (first post-baselineassessment) with further reductions through Week 12. CDAI response (CDAIdecrease �100) was demonstrated in 66% of patients and CDAI remission(CDAI5 150) was demonstrated in 46% of patients with a mean reduction atWeek 12 of 130 points. Adverse event and serious adverse event rates appeared tobe related to underlying moderate to severe Crohn’s disease. The overall safetyprofile in CD was similar to that observed in UC.Conclusion: Oral ozanimod demonstrated meaningful clinical improvements asearly as Week 4 and endoscopic improvements at Week 12 in patients withmoderate to severe CD. No new safety signals were identified.Disclosure of Interest: B.G. Feagan: Consultancy: Celgene, Directorship(s):Robarts Clinical Trials.W.J. Sandborn: Financial support for research: Celgene, Janssen, AbbVie,Prometheus Laboratories, Pfizer, Amgen, Genentech, Takeda/Consultancy:Celgene, Jansen, AbbVie, UCB Pharma, Shire, Salix, Actavis, PrometheusLaboratories, Pfizer, Amgen, Genentech, Takeda

G. D’Haens: Consultancy: Celgene. Directorship(s): Robarts Clinical Trials.Shareholder: Engene.B.G. Levesque: Directorship(s): Robarts Clinical Trials. Consultancy: TillottsPharma, Gilead, Roche, Prometheus.B.E. Skolnick: Shareholder: Celgene/other: Celgene.C. Li: Shareholder: Celgene/other: Celgene.D. Penenberg: Shareholder: Celgene/other: Celgene.R. Aranda: Shareholder: Celgene/other: Celgene.A. Olson: Shareholder: Celgene/other: Celgene.

Reference

Sandborn WJ, Feagan BG, Wolf DC, D’Haens G, et al. Ozanimod Inductionand Maintenance Treatment for Ulcerative Colitis. N Engl J Med. 2016 May5;374(18):1754–62.

OP010 EXPOSURE-RESPONSE RELATIONSHIPS FOR THEEFFECT OF UPADACITINIB ON CLINICAL AND ENDOSCOPICEFFICACY ENDPOINTS IN SUBJECTS WITH MODERATELY TOSEVERELY ACTIVE CROHN’S DISEASE – ANALYSIS OF CELESTSTUDY

M. F. Mohamed1, B. Klünder2, A. P. Lacerda3, A. A. Othman11Clinical Pharmacology And Pharmacometrics, AbbVie, North Chicago/UnitedStates of America2Clinical Pharmacology And Pharmacometrics, AbbVie Deutschland GmbH & Co.KG, Ludwigshafen am Rhein/Germany3Immunology Development, AbbVie Inc., North Chicago/United States of America

Contact E-mail Address: [email protected]: Upadacitinib (ABT-494) is an oral selective JAK1 inhibitor cur-rently in development for the treatment of several inflammatory diseases includ-ing Crohn’s disease (CD). Upadacitinib demonstrated clinical and endoscopicefficacy with an acceptable safety profile in subjects with moderately to severelyactive CD during the induction period of the Phase 2 dose-ranging CELESTstudy (NCT02365649).1

Aims & Methods: The objective of these analyses was to characterize the relation-ships between upadacitinib plasma exposures and the clinical and endoscopicefficacy endpoints in the CELEST study. The analyses datasets included datafrom 220 subjects with moderately to severely active CD who had inadequateresponse or were intolerant to immunomodulators or anti-tumor necrosis factortherapy. Subjects were randomized in a 1:1:1:1:1:1 ratio to receive 3mg twicedaily (BID), 6mg BID, 12mg BID, 24mg BID, or 24mg once daily doses ofupadacitinib immediate-release formulation, or matching placebo. Clinical effi-cacy assessments and sparse blood samples for pharmacokinetics were collectedfrom each subject over a 16-week induction period. Endoscopic evaluation wasconducted at Baseline and at Weeks 12 or 16. Clinical response and modifiedclinical remission were assessed based on the average daily very soft or liquidstool frequency and average daily abdominal pain score; and the Clinical DiseaseActivity Index (CDAI). Endoscopic response, improvement, and remission wereassessed based on Simplified Endoscopic Score for CD (SES-CD). The relation-ships between model-predicted upadacitinib plasma exposures and the differentclinical and endoscopic endpoints were evaluated using quartile plots, continu-ous-time Markov chain models for the clinical endpoints, and regression analysesfor the endoscopic endpoints. The final exposure-response models were used topredict the efficacy of selected ABT-494 regimens of interest.Results: The percentage of subjects achieving clinical response, modified clinicalremission, CDAI remission, endoscopic response, endoscopic improvement, andendoscopic remission were correlated with upadacitinib plasma exposures.Upadacitinib plasma exposures associated with 12mg BID dose achieved themajority of therapeutic benefit for clinical endpoints. The highest efficacy forendoscopic endpoints was achieved in subjects within upadacitinib plasma expo-sure quartile corresponding to 24mg BID dose. The predicted percentage ofsubjects achieving the aforementioned endpoints based on the exposure-responseanalyses is presented in Table 1 for a range of upadacitinib doses. Clinical effi-cacy was comparable between Weeks 12 and 16.

Table 1:Exposure-Response Model-Predicted Efficacy for Different UpadacitinibDosing Regimens using the Immediate-Release Formulation*

Endpoint, MedianPredicted Efficacy,% (90% PredictionInterval) Placebo 6mg BID 12mg BID 18mg BID 24mg BID

Clinical Efficacy Endpoints at Week 12Clinical Response 35 (29, 40) 52 (46, 57) 56 (50, 61) 58 (53, 63) 59 (53, 64)

Modified ClinicalRemission

12 (8, 16) 24 (18, 29) 29 (24, 34) 32 (27, 37) 34 (28, 39)

CDAI Remission 20 (15, 24) 27 (23, 32) 32 (26, 38) 34 (29, 40) 36 (31, 42)

Endoscopic Efficacy Endpoints at Week 12 or 16Endoscopic Remission 0# 10 (6, 13) 15 (11, 19) 18 (15, 22) 20 (16, 24)

Endoscopic Response 15 (11, 19) 34 (28, 39) 45 (39, 52) 52 (47, 58) 57 (50, 62)

Endoscopic Improvement 3 (1, 5) 20 (15, 25) 27 (24, 31) 33 (27, 38) 36 (29, 41)

#Placebo response for Endoscopic Remission was fixed in the model to theobserved response *Simulations for 220 subjects for each dose group ClinicalResponse: �30% reduction from baseline in abdominal pain (AP) score and/orvery soft or liquid stool frequency (SF), with neither worse than baseline

United European Gastroenterology Journal 5(5S) A5

Modified Clinical Remission: average daily SF� 2.8 and average daily AP score�1.0 with both not worse than baseline CDAI remission: Crohn’s disease activityindex 5150 Endoscopic Remission: SES-CD �4 and �2 point reduction frombaseline, no subscore 41 Endoscopic Response: �25% decrease in SES-CDfrom baseline Endoscopic Improvement: 450% decrease in SES-CD from base-line or endoscopic remissionConclusion: Upadacitinib exposures associated with 18mg BID to 24mg BID arepredicted to maximize the response for clinical and endoscopic endpoints.Disclosure of Interest: M.F. Mohamed: employee and shareholder of AbbVieB. Klünder: employee and shareholder of AbbVieA.P. Lacerda: employee and shareholder of AbbVieA.A. Othman: employee and shareholder of AbbVie

Reference

1. Safety and Efficacy of ABT-494 (upadacitinib), an oral JAK1 inhibitor, asinduction therapy in patients with Crohn’s disease: results from Celest.Sandborn WJ et al. DDW 2017 Abstract 874 h

MONDAY, OCTOBER 30, 2017 10:30-12:00FATTY LIVER DISEASE: UPDATE 2017 -ROOM A2____________________

OP011 AN ESCHERICHIA COLI PATHOGEN ISOLATED FROM ANON-ALCOHOLIC STEATOHEPATITIS PATIENT PROMOTES THEDEVELOPMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE INHIGH FAT DIET MICE

Z. Wu1, N. Wu2, J. Tan1, J. Xu1, Y. Song1, F. Zhang1, Y. L. Liu11Department Of Gastroenterology, Peking University People’s Hospital, Beijing/China2Institute Of Clinical Molecular Biology & Central Laboratory, Peking UniversityPeople’s Hospital, Beijing/China

Contact E-mail Address: [email protected]: The role of the gut microbiota in the pathogenesis of non-alcoholicfatty liver disease (NAFLD) has emerged into an important research area. Wefound that the relative abundance of Escherichia both in fecal and mucosa-asso-ciated microbiota was significantly increased in NASH patients in our formerstudy. To explore the causative role it may have in NAFLD development, weisolated one clinical Escherichia coli stain from a NASH patient’s gut mucosasample, and then evaluate the metabolic function, liver steatosis pathology andgut barrier function of NAFLD C57BL/6 mice inoculated by this clinicalEscherichia coli strain.Aims & Methods: We obtained one clinical isolate (NP1) enriched in relativeabundance 81% of the NASH patient’s gut mucosa bacteria, and identified itas Escherichia coli through biochemical tests and 16S ribosomal RNA genesequencing. To test whether NP1 can overcome this resistance to NASH bycolonizing the gut of mice, we infused 108 cells of NP1 or Lactobacillus (Lac),or Luria-Bertani (LB) culture medium as control every day for two weeks intoC57BL/6 J mice by gastric gavage, which have been fed under either normal chowdiet or high fat diet (HFD) for 12 weeks, and mice were sacrificed by 20th week.Body weight, blood glucose, systemic lipid metabolism, intestinal barrier func-tion, and hepatic inflammation and fibrosis were assessed to explore the causa-tive role of NP1 in the development of NASH.Results: We compared three groups of HFD mice, including HFDþNP1,HFDþLac and HFDþLB groups. The body weight, oral glucose tolerancetest and serum lipid profiles exhibited no significant difference among threegroups. However, HFDþNP1 group showed the worst liver pathology andthe highest NAFLD activity score (P5 0.01), compared with the HFDþLacand HFDþLB groups. What’s more, liver fibrosis was the most serious in theHFDþNP1 group, which was confirmed by Masson staining and Sirius-Redstaining. Consistent with this, the mRNA expression of MCP-1 (P5 0.05), IL-6 (P5 0.05) and TNF-� (P5 0.01) in liver of HFDþNP1 group were signifi-cantly higher than the other two groups, and the mRNA expression of IL-10(P5 0.01) were the lowest in HFDþNP1 group. Besides, the gut mucosa ofHFDþNP1 mice developed inflammation phenotype with the highest level ofIL-6 (P5 0.01) and the lowest level of IL-10 (P5 0.01) by the RT-PCR results.The mRNA expression of ZO-1 (P5 0.05) and Occludin (P5 0.01) in gutmucosa of HFDþNP1 group were reduced, indicating the dysfunction of gutbarrier. The three groups fed with normal chow diet did not show hepatic inflam-mation and fibrosis.Conclusion: The HFD mice with the strain of Escherichia coli NP1 isolated fromthe NASH patient shows aggravated intestinal inflammatory conditions. What’smore, strain of Escherichia coli NP1 promotes hepatic inflammation and fibrosis,without affecting the systemic lipid or glucose metabolism, whereas the controlmice on normal chow diet don’t exhibit the same disease phenotypes. This worksuggests that the overgrowth of Escherichia coli gut bacterium isolated fromNASH patient may be a contributing factor to NAFLD via injuring the intestinalbarrier, rather than a bystander.Disclosure of Interest: All authors have declared no conflicts of interest.

OP012 DIET-DEPENDENT ACID LOAD IS ASSOCIATED WITHNON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IN THEGENERAL POPULATION: THE ROTTERDAM STUDY

L. J.M. Alferink1, J. C. Kiefte- De Jong2, N. S. Erler3, J. D. Schoufour4, E.J. Hoorn5, M. a. Ikram4, H. L. a. Janssen6, H. J. Metselaar1, O. H. Franco4,S. Darwish Murad11Gastroenterology And Hepatology, Erasmus Medical Center, Rotterdam/Netherlands2Global Public Health, Leiden University College, Leiden/Netherlands3Biostatistics, Erasmus Medical Center, Rotterdam/Netherlands4Epidemiology, Erasmus Medical Center, Rotterdam/Netherlands5Internal Medicine, Division Of Nephrology And Transplantation, ErasmusMedical Center, Rotterdam/Netherlands6Hepatology, Toronto Centre for Liver Disease, Toronto/Canada/ON

Contact E-mail Address: [email protected]: A healthy lifestyle is the cornerstone of treatment in patients withNAFLD and likewise, an unhealthy diet is implicated in the etiology of thisdisease. We recently found high animal protein intake to be associated withNAFLD and we hypothesize that this may be explained by increased diet-depen-dent acid load.Aims & Methods: The aim of this study is to examine if dietary acid load isassociated with NAFLD. The Rotterdam Study is an ongoing prospective popu-lation-based cohort study in a suburb of Rotterdam, The Netherlands. Based ona validated 389-item food frequency questionnaire, the dietary acid load wasestimated by calculating the net endogenous acid production (NEAP, using pro-tein intake and potassium), potential renal acid load (PRAL, using protein,phosphorus, potassium, calcium and magnesium), and animal-to-potassiumratio (A:P). Subsequently, these determinants were analysed in quartiles (Q4vs. Q1). NAFLD was defined as presence of steatosis on ultrasound in absenceof steatogenic drugs, viral hepatitis and alcohol abuse. Logistic regression wasperfo

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