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Original article
Natural disease course of Crohn’s disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study
  1. Johan Burisch1,
  2. Gediminas Kiudelis2,
  3. Limas Kupcinskas2,3,
  4. Hendrika Adriana Linda Kievit4,
  5. Karina Winther Andersen5,
  6. Vibeke Andersen5,6,
  7. Riina Salupere7,
  8. Natalia Pedersen8,
  9. Jens Kjeldsen9,
  10. Renata D’Incà10,
  11. Daniela Valpiani11,
  12. Doron Schwartz12,
  13. Selwyn Odes12,
  14. Jóngerð Olsen13,
  15. Kári Rubek Nielsen13,
  16. Zsuzsanna Vegh14,
  17. Peter Laszlo Lakatos14,15,
  18. Alina Toca16,
  19. Svetlana Turcan16,
  20. Konstantinos H Katsanos17,
  21. Dimitrios K Christodoulou17,
  22. Mathurin Fumery18,
  23. Corinne Gower-Rousseau19,20,
  24. Stefania Chetcuti Zammit21,
  25. Pierre Ellul21,
  26. Carl Eriksson22,
  27. Jonas Halfvarson22,
  28. Fernando Jose Magro23,24,
  29. Dana Duricova25,
  30. Martin Bortlik25,26,
  31. Alberto Fernandez27,
  32. Vicent Hernández28,
  33. Sally Myers29,
  34. Shaji Sebastian29,
  35. Pia Oksanen30,31,
  36. Pekka Collin31,
  37. Adrian Goldis32,
  38. Ravi Misra33,
  39. Naila Arebi33,
  40. Ioannis P Kaimakliotis34,
  41. Inna Nikuina35,
  42. Elena Belousova35,
  43. Marko Brinar36,
  44. Silvija Cukovic-Cavka36,
  45. Ebbe Langholz37,
  46. Pia Munkholm1
  47. for the Epi-IBD group
    1. 1 Department of Gastroenterology, Nordsjællands Hospital, University of Copenhagen, Frederikssund, Denmark
    2. 2 Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
    3. 3 Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
    4. 4 Department of Medicine, Herning Central Hospital, Herning, Denmark
    5. 5 Medical Department, Regional Hospital of Viborg, Viborg, Midtjylland, Denmark
    6. 6 Focused research unit for Molecular Diagnostic and Clinical Research (MOK), IRS-Center Sonderjylland, Hospital of Southern Jutland, Aabenraa, Denmark
    7. 7 Division of Gastroenterology, Tartu University Hospital, University of Tarty, Tartu, Estonia
    8. 8 Gastroenterology Department, Slagelse Hospital, Slagelse, Sjaelland, Denmark
    9. 9 Gastroenterology Department, Odense University Hospital, Odense, Denmark
    10. 10 Department of Surgical, Oncological and Gastroenterological Sciences, Azienda, University of Padua, Padova, Italy
    11. 11 U.O. Gastroenterologia ed Endoscopia digestiva, Hospital Morgagni Pierantoni, Forlì, Italy
    12. 12 Department of Gastroenterology and Hepatology, Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel
    13. 13 Medical Department, The National Hospital of the Faroe Islands, Thorshavn, Faroe Islands
    14. 14 1st Department of Medicine, Semmelweis University, Budapest, Hungary
    15. 15 Division of Gastroenterology, McGill University Health Center, Montreal, Canada
    16. 16 Department of Gastroenterology, State University of Medicine and Pharmacy of the Republic of Moldova, Chisinau, Republic of Moldova
    17. 17 Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece
    18. 18 Gastroenterology Unit, Epimad Registry, CHU Amiens Sud, Avenue Laennec-Salouel, Amiens University Hospital, Amiens, France
    19. 19 Public Health, Epidemiology and Economic Health, Registre Epimad, Lille University and Hospital, Lille, France
    20. 20 Lille Inflammation Research International Center LIRIC, Lille University, Lille, France
    21. 21 Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
    22. 22 Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
    23. 23 Department of Gastroenterology, Centro Hospitalar de São João EPE, Porto, Portugal
    24. 24 Department of Biomedicine, Institute of Pharmacology, Faculty of Medicine of Porto University, Porto, Portugal
    25. 25 IBD Clinical and Research Centre, ISCARE, Prague, Czech Republic
    26. 26 Institute of Pharmacology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
    27. 27 Department of Gastroenterology, Hospital POVISA, Vigo, Spain
    28. 28 Department of Gastroenterology, Hospital Alvaro Cunqueiro. Instituto Investigación Sanitaria Galicia Sur. EOXI de Vigo, Vigo, Spain
    29. 29 IBD Unit, Hull and East Yorkshire NHS Trust, Hull, UK
    30. 30 Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
    31. 31 University of Tampere, Tampere, Finland
    32. 32 Clinic of Gastroenterology, University of Medicine ‘Victor Babes’, Timisoara, Romania
    33. 33 IBD Department, Imperial College London, London, UK
    34. 34 Nicosia private practice, Nicosia, Cyprus
    35. 35 Department of Gastroenterology, Moscow Regional Research Clinical Institute, Moscow, Russian Federation
    36. 36 Division of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia
    37. 37 Department of Gastroenterology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
    1. Correspondence to Dr Johan Burisch, Department of Gastroenterology, North Zealand University Hospital, 3600 Frederikssund, Denmark; burisch{at}


    Objective The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn’s disease (CD).

    Design Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.

    Results In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).

    Conclusion Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

    • crohn’s disease
    • surgery for Ibd
    • epidemiology

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    • Contributors All authors participated in the study design and data acquisition, have critically reviewed the draft manuscript for content and approved the final version for publication. JB had full access to the data in the study and takes full responsibility for its veracity and statistical analysis. JB and PM analysed and interpreted the data. JB drafted the manuscript. PM supervised the study.

    • Funding Unrestricted grant support has been received from Kirsten og Freddy Johansens Fond as well as from Nordsjællands Hospital Forskningsråd.

    • Disclaimer The study sponsors have made no contributions to the study design, analysis, data interpretation or publication.

    • Competing interests JB: consulting fees from Celgene, Janssen-Cilag, AbbVie A/S and Ferring and lecture fees from Abbvie A/S, Pfizer, MSD and Takeda Pharma A/S. VA: consultancy for Janssen and MSD. RS: consulting fees and/or lecture fees from AbbVie, MSD, Takeda, Janssen-Cilag. RD’I: consulting fees from Abbvie, Biocure and lecture fees from Takeda and Mundipharma. MF: speaker/lecture fees for Abbvie, Ferring, MSD, Takeda, Boehringer and Hospira. CG-R: lecture fees from Takeda, MSD, Ferring and Tillots. CE: lecture fees from Takeda. JH: research grants from Janssen, MSD and Takeda and lecture and/or consultancy fees from Abbvie, Cellgene, Ferring, Hospira, Janssen, Medivir, MSD, Pfizer, Vifor Pharma, Takeda and Tillotts Pharma. EL: lecture or consultancy fees from MSD, Abbvie and Ferring Pharmaceuticals. DD: lecture or consultancy fees from AbbVie, Takeda and Janssen. NA: lecture fees from MSD and Jansen. VH: personal fees, non-financial support and other from MSD, AbbVie, Ferring, Faes Farma, Shire, Falk Pharma, Tillots, Otsuka, Hospira Biologicals, Takeda, Jansen and Kernpharma Biologics. AF: personal fees and non-financial support from MSD, AbbVie, Shire and Tillots. SČ-Č: lecture fees from Takeda, MSD, Abbvie.

    • Ethics approval All centres obtained approval from their respective, local ethical committees.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Collaborators Ola Niewiadomski (Australia), Sally Bell (Australia), Niksa Turk (Croatia), Silvija Cukovic-Cavka (Croatia), Ioannis Kaimakliotis (Cyprus), Anastasia Nicolaou (Cyprus), Dana Duricova (Czech Republic), Milan Lukas (Czech Republic), Martin Bortlík (Czech Republic), Olga Shonová (Czech Republic), Johan Burisch (Denmark), Pia Munkholm (Denmark), Ebbe Langholz (Denmark), Birgitte Blichfeldt (Denmark), Dorte Marker (Denmark), Katrine Carlsen (Denmark), Petra Weimers (Denmark), Natalia Pedersen (Denmark), Jens Kjeldsen (Denmark), Clays Aalykke (Denmark), Jens Frederik Dahlerup (Denmark), Karen Kudsk (Denmark), Vibeke Andersen (Denmark), Ida Vind (Denmark), Niels Thorsgaard (Denmark), Riina Salupere (Estonia), Jóngerð Olsen (Faroe Islands), Kári Rubek Nielsen (Faroe Islands), Pia Oksanen (Finland), Pekka Collin (Finland), Konstantinnos H Katsanos (Greece), Dimitrios K Christodoulou (Greece), Alexandros Skamnelos (Greece), Dimitrios Politis (Greece), Karin Ladefoged (Greenland), Peter Laszlo Lakatos (Hungary), Zsuzsanna Vegh (Hungary), Laszlo Lakatos (Hungary), Peterne Demenyi (Hungary), Szabina Nemethne Kramli (Hungary), Colm O’Morain (Ireland), Giualia Dal Piaz (Italy), Alessia Santini (Italy), Giulia Girardin (Italy), Renata D’Inca (Italy), Doron Schwartz (Israel), Selwyn Odes (Israel), Limas Kupcinskas (Lithuania), Laimas Jonaitis (Lithuania), Gediminas Kiudelis (Lithuania), Irena Valantiene (Lithuania), Romanas Zykus (Lithuania).