A Novel 8-Predictors Signature to Predict Complicated Disease Course in Pediatric-onset Crohn’s Disease: A Population-based Study
Author:
Sarter Hélène12, Savoye Guillaume3, Marot Guillemette45, Ley Delphine26, Turck Dominique26, Hugot Jean-Pierre78, Vasseur Francis4, Duhamel Alain4, Wils Pauline29, Princen Fred10, Colombel Jean-Frédéric11, Gower-Rousseau Corinne1212, Fumery Mathurin13ORCID, Al Hameedi R, Al Khatib M, Al Turk S, Agoute E, Andre J M, Antonietti M, Aouakli A, Armand A, Armengol-Debeir L, Aroichane I, Assi F, Aubet J P, Auxenfants E, Avram A, Ayafi-Ramelot F, Azzouzi K, Bankovski D, Barbry B, Bardoux N, Baron P, Baudet A, Bayart P, Bazin B, Bebahani A, Becqwort J P, Bellati S, Benet V, Benali H, Benard C, Benguigui C, Ben Soussan E, Bental A, Berkelmans I, Bernet J, Bernou K, Bernou-Dron C, Bertot P, Bertiaux-Vandaële N, Bertrand V, Billoud E, Biron N, Bismuth B, Bleuet M, Blondel F, Blondin V, Bobula M, Bohon P, Bondjemah V, Boniface E, Bonkovski D, Bonnière P, Bonvarlet E, Bonvarlet P, Boruchowicz A, Bostvironnois R, Boualit M, Bouazza A, Bouche B, Boudaillez C, Bourgeaux C, Bourgeois M, Bourguet A, Bourienne A, Boutaleb H, Bouthors A, Branche J, Bray G, Brazier F, Breban P, Bridenne M, Brihier H, Bril L, Brung-Lefebvre V, Bulois P, Burgiere P, Butel J, Canva J Y, Canva-Delcambre V, Capron J P, Cardot F, Carette S, Carpentier P, Cartier E, Cassar J F, Cassagnou M, Castex J F, Catala P, Cattan S, Catteau S, Caujolle B, Cayron G, Chandelier C, Chantre M, Charles J, Charneau T, Chavance-Thelu M, Cheny A, Chirita D, Choteau A, Claerbout J F, Clergue P Y, Coevoet H, Cohen G, Collet R, Colin M, Colombel J F, Coopman S, Cordiez L, Corvisart J, Cortot A, Couttenier F, Crinquette J F, Crombe V, Dadamessi I, Daoudi H, Dapvril V, Davion T, Dautreme S, Debas J, Decoster S, Degrave N, Dehont F, Delatre C, Delcenserie R, Delesalle D, Delette O, Delgrange T, Delhoustal L, Delmotte J S, Demmane S, Deregnaucourt G, Descombes P, Desechalliers J P, Desmet P, Desreumaux P, Desseaux G, Desurmont P, Devienne A, Devouge E, Devred M, Devroux A, Dewailly A, Dharancy S, Di Fiore A, Djedir D, Djedir R, Doleh W, Dreher-Duwat M L, Dubois R, Duburque C, Ducatillon P, Duclay J, Ducrocq B, Ducrot F, Ducrotte P, Dufilho A, Duhamel C, Dujardin D, Dumant-Forest C, Dupas J L, Dupont F, Duranton Y, Duriez A, Duveau N, El Achkar K, El Farisi M, Elie C, Elie-Legrand M C, Elkhaki A, Eoche M, Essmaeel E, Evrard D, Evrard J P, Fatome A, Filoche B, Finet L, Flahaut M, Flamme C, Foissey D, Fournier P, Foutrein-Comes M C, Foutrein P, Fremond D, Frere T, Fumery M, Gallais P, Gamblin C, Ganga S, Gerard R, Geslin G, Gheyssens Y, Ghossini N, Ghrib S, Gilbert T, Gillet B, Godart D, Godard P, Godchaux J M, Godchaux R, Goegebeur G, Goria O, Gottrand F, Gower P, Grandmaison B, Groux M, Guedon C, Guerbeau L, Gueroult-Dero M, Guillard J F, Guillem L, Guillemot F, Guimberd D, Haddouche B, Hakim S, Hanon D, Hautefeuille V, Heckestweiller P, Hecquet G, Hedde J P, Hellal H, Henneresse P E, Heyman B, Heraud M, Herve S, Hochain P, Houssin-Bailly L, Houcke P, Huguenin B, Iobagiu S, Istanboli S, Ivanovic A, Iwanicki-Caron I, Janicki E, Jarry M, Jeu J, Joly J P, Jonas C, Jouvenet A, Katherin F, Kerleveo A, Khachfe A, Kiriakos A, Kiriakos J, Klein O, Kohut M, Kornhauser R, Koutsomanis D, Laberenne J E, Lacotte E, Laffineur G, Lagarde M, Lalanne A, Lalieu A, Lannoy P, Lapchin J, Laprand M, Laude D, Leblanc R, Lecieux P, Lecleire S, Leclerc N, Le Couteulx C, Ledent J, Lefebvre J, Lefiliatre P, Le Goffic C, Legrand C, Le Grix A, Lelong P, Leluyer B, Lemaitre C, Lenaerts C, Lepeut G, Lepileur L, Leplat A, Lepoutre-Dujardin E, Leroi H, Leroy M Y, Le Roy P, Lesage B, Lesage J P, Lesage X, Lesage J, Lescanne-Darchis I, Lescut J, Lescut D, Leurent B, Levy P, Lhermie M, Libier L, Lion A, Lisambert B, Loge I, Loire F, Loreau J, Louf S, Louvet A, Lubret L, Luciani M, Lucidarme D, Lugand J, Macaigne O, Maetz D, Maillard D, Mancheron H, Manolache O, Marks-Brunel A B, Marre C, Marti R, Martin F, Martin G, Marzloff E, Mathurin P, Mauillon J, Maunoury V, Maupas J L, Medam Djomo M A, Mechior C, Melki Z, Mesnard B, Metayer P, Methari L, Meurisse B, Meurisse F, Michaud L, Mirmaran X, Modaine P, Monthe A, Morel L, Mortier P E, Moulin E, Mouterde O, Mozziconaci N, Mudry J, Nachury M, Ngo M D, N’Guyen Khac E, Notteghem B, Ollevier V, Ostyn A, Ouraghi A, Oussadou B, Ouvry D, Paillot B, Painchart C, Panien-Claudot N, Paoletti C, Papazian A, Parent B, Pariente B, Paris J C, Patrier P, Paupard T, Pauwels B, Pauwels M, Penninck E, Petit R, Piat M, Piotte S, Plane C, Plouvier B, Pollet E, Pommelet P, Pop D, Pordes C, Pouchain G, Prades P, Prevost A, Prevost J C, Quartier G, Quesnel B, Queuniet A M, Quinton J F, Rabache A, Rabelle P, Raclot G, Ratajczyk S, Rault D, Razemon V, Reix N, Renaut-Vantroys T, Revillion M, Riachi G, Richez C, Robinson P, Rodriguez J, Roger J, Roux J M, Rudelli A, Saber A, Savoye G, Schlossberg P, Sefrioui D, Segrestin M, Seguy D, Seminur C, Serin M, Seryer A, Sevenet F, Shekh N, Silvie J, Simon V, Spyckerelle C, Talbodec N, Tavernier N, Tchandeu H, Techy A, Thelu J L, Thevenin A, Thiebault H, Thomas J, Thorel J M, Thuillier C, Tielman G, Tode M, Toisin J, Tonnel J, Touchais J Y, Toumelin P, Touze Y, Tranvouez J L, Triplet C, Triki N, Turck D, Uhlen S, Vaillant E, Valmage C, Vanco D, Vandaele-Bertiaux N, Vandamme H, Vanderbecq E, Vander Eecken E, Vandermolen P, Vandevenne P, Vandeville L, Vandewalle A, Vandewalle C, Vaneslander P, Vanhoove J P, Vanrenterghem A, Vanveuren C, Varlet P, Vasies I, Verbiese G, Verlynde J, Vernier-Massouille G, Vermelle P, Verne C, Vezilier-Cocq P, Vigneron B, Vincendet M, Viot J, Voiment Y M, Wacrenier A, Waeghemaecker L, Wallez J Y, Wantiez M, Wartel F, Weber J, Willocquet J L, Wizla N, Wolschies E, Zaharia O, Zaoui S, Zalar A, Zaouri B, Zellweger A, Ziade C, Beaugerie L, Allez M, Ruemmele F, Lamer A, Roy M,
Affiliation:
1. Lille Hospital and University, Public Health, Epidemiology and Economic Health, EPIMAD registry, Regional house of clinical research , F-59000 Lille , France 2. University of Lille, Inserm, CHU Lille, U1286, INFINITE, Institute for Translational Research in Inflammation , F-59000 Lille , France 3. Rouen Hospital and University, Gastroenterology Unit, EPIMAD registry , Rouen , France 4. University of Lille, CHU Lille, ULR 2694-METRICS: Evaluation des Technologies de Santé et des Pratiques Médicales , F-59000 Lille , France 5. Inria Lille Nord Europe, Modal , Lille , France 6. Lille University Jeanne de Flandre Children’s Hospital and Faculty of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics , Lille , France 7. Centre de Recherche sur l’Inflammation, UMR1149 INSERM et Université de Paris , France 8. Department of Pediatric Gastroenterology, Hôpital Robert Debré, Assistance Publique Hôpitaux de Paris (AP-HP) , Paris , France 9. Gastroenterology Unit, Lille Hospital and University , Lille , France 10. Prometheus Laboratories , San Diego, California 11. Icahn School of Medicine at Mount Sinai, Division of Gastroenterology , New York , USA 12. Research and Public Health Unit, Reims University & Hospital, Robert-Debré Hospital , Reims , France 13. Amiens Hospital and University, Gastroenterology Unit, EPIMAD Registry, and PeriTox , UMR I-01, Amiens , France
Abstract
Abstract
Background
The identification of patients at high risk of a disabling disease course would be invaluable in guiding initial therapy in Crohn’s disease (CD). Our objective was to evaluate a combination of clinical, serological, and genetic factors to predict complicated disease course in pediatric-onset CD.
Methods
Data for pediatric-onset CD patients, diagnosed before 17 years of age between 1988 and 2004 and followed more than 5 years, were extracted from the population-based EPIMAD registry. The main outcome was defined by the occurrence of complicated behavior (stricturing or penetrating) and/or intestinal resection within the 5 years following diagnosis. Lasso logistic regression models were used to build a predictive model based on clinical data at diagnosis, serological data (ASCA, pANCA, anti-OmpC, anti-Cbir1, anti-Fla2, anti-Flax), and 369 candidate single nucleotide polymorphisms.
Results
In total, 156 children with an inflammatory (B1) disease at diagnosis were included. Among them, 35% (n = 54) progressed to a complicated behavior or an intestinal resection within the 5 years following diagnosis. The best predictive model (PREDICT-EPIMAD) included the location at diagnosis, pANCA, and 6 single nucleotide polymorphisms. This model showed good discrimination and good calibration, with an area under the curve of 0.80 after correction for optimism bias (sensitivity, 79%, specificity, 74%, positive predictive value, 61%, negative predictive value, 87%). Decision curve analysis confirmed the clinical utility of the model.
Conclusions
A combination of clinical, serotypic, and genotypic variables can predict disease progression in this population-based pediatric-onset CD cohort. Independent validation is needed before it can be used in clinical practice.
Funder
Institut National de la Santé et de la Recherche Médicale Programme Hospitalier de Recherche Clinique Inter-regional
Publisher
Oxford University Press (OUP)
Subject
Gastroenterology,Immunology and Allergy
Cited by
1 articles.
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