A Novel 8-Predictors Signature to Predict Complicated Disease Course in Pediatric-onset Crohn’s Disease: A Population-based Study
Authors: Sarter Hélène , Savoye Guillaume , Marot Guillemette , Ley Delphine , Turck Dominique , Hugot Jean-Pierre , Vasseur Francis , Duhamel Alain , Wils Pauline , Princen Fred , Colombel Jean-Frédéric , Gower-Rousseau Corinne , Fumery Mathurin ,   EPIMAD study group, 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 
Published: June 2023

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.