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MICI et facteurs environnementaux: études épidémiologiques

Workpackage : WP1

The aim of our team is to work on IBD epidemiology through descriptive and analytical epidemiological studies. This objective is using the largest population-based study on IBD in the world that we built in 1988, the EPIMAD registry. The EPIMAD registry covers a large area of Northern France with almost 6 million inhabitants representing 9.3% of the entire French population. Since 30 years, we recorded near of 1000 new IBD cases per year. The major data source is represented by all adult and pediatric gastroenterologists (n=254) consulting in this area whatever their type of practice (private, public or both). Currently, near of 29000 incident IBD cases are recorded in our database.


Research topics

For the period 2013-2018, the activity of our team has led to the publication of around 50 original articles and 20 reviews with 60% in A and B ranks. Among them, descriptive epidemiological studies on the EPIMAD registry allowed us to assess incidence of paediatric-onset IBD and very-early-onset IBD. Pediatric-onset IBD (< 17 years at diagnosis) involved a total of 1350 patients over a 24-year period (1988-2011) representing 8.3% of all incident IBD cases. The major finding from our study is that the incidence of paediatric-onset IBD doubled during a 24 year-period. This was more marked in adolescents than in children under 10 years. The large use of antibiotics and the dramatic decrease of appendectomy in our geographical area could play a role as environmental risk factors, at least in part, in these modifications in the incidence of pediatric-onset IBD in Northern France. (Ghione et al. Am J Gastroenterol 2018).

We then compared changes over time in the incidence and phenotype at diagnosis between two groups of patients according to age at IBD diagnosis: very-early-onset IBD (VEO-IBD) (< 6 years at diagnosis) and early-onset IBD [EO-IBD] (diagnosed between 6 and 16 years of age). In this large population-based cohort, the incidence of VEO-IBD was low and stable from 1988 to 2011, with a specific clinical presentation. These results suggest a probable genetic origin for VEO-IBD, whereas the increase in EO-IBD might be linked to environmental factors. (Bequet et al. JCC 2017).

We performed analytical epidemiology on 2 cohorts of patients from the EPIMAD registry; the paediatric-onset UC, to study phenotype and elderly-onset (> 60 years at diagnosis) IBD to study their natural history (Charpentier et al. Gut 2014) and to provide safety data on surgical options. We showed that in children, ulcerative proctitis (UP) is a frequent location of and not a minor disease. Indeed, we found that at UC diagnosis in children, 25% of them was localized to the rectum. Compared with more extensive UC locations, risks for colonic extension, anti-TNF-α therapy and colectomy were similar in UP. (Hochart A et al. Gut 2017).

We showed in the elderly-onset IBD cohort that surgery, especially in emergency setting and severe ulcerative colitis attacks, were associated with early post-operative complications especially infections (Sacleux et al. Aliment Pharmacol Ther 2018). In this elderly-onset IBD cohort, we reported that after a median time follow up of six years (5,598 patient-years), the overall cancer risk in this population was not significantly different from that of the general population. Our data reinforce the peculiarity of elderly-onset IBD (Cheddani et al. Am J Gastroenterol 2016).

Inflammatory Bowel Diseases are a major cause of disability in young adults. We described for the first time the disability status (Disability Index (IBD-DI)) in a population-based cohort of patients with IBD, using a thorough methodology including all steps (item reduction and data structure, construct validity, internal consistency, inter and intra-observer reliability) of quantitative validation. IBD-DI score ranged from 0 to 91 (possible maximum score of 100) with a mean of IBD-DI was 35.3 (± SD 20.5) and associated risk factors for high IBD-DI scores were female gender, long disease duration, and high clinical disease activity. (Gower-Rousseau et al. Gut 2017). Joining an international Taskforce, we just published the self-Independent Validation of the Self-Report Version of the IBD Disability Index. (Shafer et al. Inflamm Bowel Dis 2018).

Finally, we have integrated a part of the population monitored by Epimad (Somme area; 500 000 of inhabitants) into the European cohort of patients with IBD built by the Epidemiological Taskforce of European Crohn’s and Colitis Organization. (Burisch J et al. Gut 2018) to participate to a European IBD cohort to better know the diagnosis and therapeutic managements of IBD in different countries of Europe.

To address the factors implicated in the identified clusters of very high incidence of IBD, we build a multidisciplinary, transversal and international consortium gathering epidemiologists, gastroenterologists, biostatistician, geographers, historian, toxicologists, biologists, dentists, and specialists in the ecology of water and air. This HEROIC (Highliting EnviROnmental features in epidemIc areas of Crohn’s disease) consortium will represent the foundation of the epidemiological project for the next contract.



FG PaperJLD 2011 1

Dramatic Increase in Incidence of Ulcerative Colitis and Crohn's Disease (1988-2011): A Population-Based Study of French Adolescents
Ghione S, Sarter H, Fumery M, Armengol-Debeir L, Savoye G, Ley D, Spyckerelle C, Pariente B, Peyrin-Biroulet L, Turck D, Gower-Rousseau C; Epimad Group.
Am J Gastroenterol 2018 Feb;113(2):265-272. doi: 10.1038/ajg.2017.2284

FG PaperJLD 2011 1

Validation of the Inflammatory Bowel Disease Disability Index in a population-based cohort
Gower-Rousseau C, Sarter H, Savoye G, Tavernier N, Fumery M, Sandborn WJ, Feagan BG, Duhamel A, Guillon-Dellac N, Colombel JF, Peyrin-Biroulet L; International Programme to Develop New Indexes for Crohn's Disease (IPNIC) group; International Programme to Develop New Indexes for Crohn's Disease (IPNIC) group.
Gut 2017 Apr;66(4):588-596. doi: 10.1136/gutjnl-2015-310151.

FG PaperJLD 2011 1

Cancer in Elderly Onset Inflammatory Bowel Disease: A Population-Based Study
Cheddani H, Dauchet L, Fumery M, Charpentier C, Marie Bouvier A, Dupas JL, Pariente B, Peyrin-Biroulet L, Savoye G, Gower-Rousseau C.
Am J Gastroenterol 2016 Oct;111(10):1428-1436. doi: 10.1038/ajg.2016.304

FG PaperJLD 2011 1

Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study
Charpentier C, Salleron J, Savoye G, Fumery M, Merle V, Laberenne JE, Vasseur F, Dupas JL, Cortot A, Dauchet L, Peyrin-Biroulet L, Lerebours E, Colombel JF, Gower-Rousseau C
Gut 2014 Mar;63(3):423-32. doi: 10.1136/gutjnl-2012-303864

FG PaperJLD 2011 1

Mapping of inflammatory bowel disease in northern France: spatial variations and relation to affluence
Declercq C, Gower-Rousseau C, Vernier-Massouille G, Salleron J, Baldé M, Poirier G, Lerebours E, Dupas JL, Merle V, Marti R, Duhamel A, Cortot A, Salomez JL, Colombel JF
Inflamm Bowel Dis 2010 May;16(5):807-12. doi: 10.1002/ibd.21111.

FG PaperJLD 2011 1

The natural history of pediatric ulcerative colitis: a population-based cohort study
Gower-Rousseau C, Dauchet L, Vernier-Massouille G, Tilloy E, Brazier F, Merle V, Dupas JL, Savoye G, Baldé M, Marti R, Lerebours E, Cortot A, Salomez JL, Turck D, Colombel JF
Am J Gastroenterol 2009 Aug;104(8):2080-8. doi: 10.1038/ajg.2009.1774

FG PaperJLD 2011 1

Natural history of pediatric Crohn's disease: a population-based cohort study
Vernier-Massouille G, Balde M, Salleron J, Turck D, Dupas JL, Mouterde O, Merle V, Salomez JL, Branche J, Marti R, Lerebours E, Cortot A, Gower-Rousseau C, Colombel JF
Gastroenterology 2008 Oct;135(4):1106-13. doi: 10.1053/j.gastro.2008.06.079

FG PaperJLD 2011 1

Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G.
Nature 2001 May 31;411(6837):599-603

FG PaperJLD 2011 1

Mapping of a susceptibility locus for Crohn's disease on chromosome 16
Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, Naom I, Dupas JL, Van Gossum A, Orholm M, Bonaiti-Pellie C, Weissenbach J, Mathew CG, Lennard-Jones JE, Cortot A, Colombel JF, Thomas GG.
Nature 1996 Feb 29;379(6568):821-33