A Novel 8-Predictors Signature to Predict Complicated Disease Course in Pediatric-onset Crohn’s Disease: A Population-based Study
Hélène Sarter
(1, 2)
,
Guillaume Savoye
(3, 4, 5, 6)
,
Guillemette Marot
(7, 8)
,
Delphine Ley
(1, 2)
,
Dominique Turck
(2)
,
Jean-Pierre Hugot
,
Francis Vasseur
(7)
,
Alain Duhamel
(7)
,
Pauline Wils
(1, 2)
,
Fred Princen
,
Jean-Frédéric Colombel
(9)
,
Corinne Gower-Rousseau
(10, 2)
,
Mathurin Fumery
(11, 12, 13)
,
A Baudet
,
P Bayart
,
B Bazin
,
A Bebahani
,
J Becqwort
,
S Bellati
,
V Benet
,
H Benali
,
C Benard
,
C Benguigui
,
E Ben Soussan
,
A Bental
,
I Berkelmans
,
J Bernet
,
K Bernou
,
C Bernou-Dron
,
P Bertot
,
N Bertiaux-Vandaële
,
V Bertrand
,
E Billoud
,
N Biron
,
B Bismuth
,
M Bleuet
,
F Blondel
,
V Blondin
,
M Bobula
,
P Bohon
,
V Bondjemah
,
E Boniface
,
D Bonkovski
,
P Bonnière
,
E Bonvarlet
,
P Bonvarlet
,
A Boruchowicz
,
R Bostvironnois
,
M Boualit
,
A Bouazza
,
B Bouche
,
C Boudaillez
,
C Bourgeaux
,
M Bourgeois
,
A Bourguet
,
A Bourienne
,
H Boutaleb
,
A Bouthors
,
J Branche
,
G Bray
,
F Brazier
,
P Breban
,
M Bridenne
,
H Brihier
,
L Bril
,
V Brung-Lefebvre
,
P Bulois
,
P Burgiere
,
J Butel
,
J Canva
,
V Canva-Delcambre
,
J Capron
,
F Cardot
,
S Carette
,
P Carpentier
,
E Cartier
,
J Cassar
,
M Cassagnou
,
J Castex
,
P Catala
,
S Cattan
,
S Catteau
,
B Caujolle
,
G Cayron
,
C Chandelier
,
M Chantre
,
J Charles
,
T Charneau
,
M Chavance-Thelu
,
A Cheny
,
D Chirita
,
A Choteau
,
J Claerbout
,
P Clergue
,
H Coevoet
,
G Cohen
,
R Collet
,
M Colin
,
J Colombel
,
S Coopman
,
L Cordiez
,
J Corvisart
,
A Cortot
,
F Couttenier
,
J Crinquette
,
V Crombe
,
I Dadamessi
,
H Daoudi
,
V Dapvril
,
T Davion
,
S Dautreme
,
J Debas
,
S Decoster
,
N Degrave
,
F Dehont
,
C Delatre
,
R Delcenserie
,
D Delesalle
,
O Delette
,
T Delgrange
,
L Delhoustal
,
J Delmotte
,
S Demmane
,
G Deregnaucourt
,
P Descombes
,
J Desechalliers
,
P Desmet
,
P Desreumaux
,
G Desseaux
,
P Desurmont
,
A Devienne
,
E Devouge
,
M Devred
,
A Devroux
,
A Dewailly
,
S Dharancy
,
A Di Fiore
,
D Djedir
,
R Djedir
,
W Doleh
,
M Dreher-Duwat
,
R Dubois
,
C Duburque
,
P Ducatillon
,
J Duclay
,
B Ducrocq
,
F Ducrot
,
P Ducrotte
,
A Dufilho
,
C Duhamel
,
D Dujardin
,
C Dumant-Forest
,
J Dupas
,
F Dupont
,
Y Duranton
,
A Duriez
,
N Duveau
,
K El Achkar
,
M El Farisi
,
C Elie
,
M Elie-Legrand
,
A Elkhaki
,
M Eoche
,
E Essmaeel
,
D Evrard
,
J Evrard
,
A Fatome
,
B Filoche
,
L Finet
,
M Flahaut
,
C Flamme
,
D Foissey
,
P Fournier
,
M Foutrein-Comes
,
P Foutrein
,
D Fremond
,
T Frere
,
P Gallais
,
C Gamblin
,
S Ganga
,
R Gerard
,
G Geslin
,
Y Gheyssens
,
N Ghossini
,
S Ghrib
,
T Gilbert
,
B Gillet
,
D Godart
,
P Godard
,
J Godchaux
,
R Godchaux
,
G Goegebeur
,
O Goria
,
F Gottrand
,
P Gower
,
B Grandmaison
,
M Groux
,
C Guedon
,
L Guerbeau
,
M Gueroult-Dero
,
J Guillard
,
L Guillem
,
F Guillemot
,
D Guimberd
,
B Haddouche
,
S Hakim
,
D Hanon
,
V Hautefeuille
,
P Heckestweiller
,
G Hecquet
,
J Hedde
,
H Hellal
,
P Henneresse
,
B Heyman
,
M Heraud
,
S Herve
,
P Hochain
,
L Houssin-Bailly
,
P Houcke
,
B Huguenin
,
S Iobagiu
,
S Istanboli
,
A Ivanovic
,
I Iwanicki-Caron
,
E Janicki
,
M Jarry
,
J Jeu
,
J Joly
,
C Jonas
,
A Jouvenet
,
F Katherin
,
A Kerleveo
,
A Khachfe
,
A Kiriakos
,
J Kiriakos
,
O Klein
,
M Kohut
,
R Kornhauser
,
D Koutsomanis
,
J Laberenne
,
E Lacotte
,
G Laffineur
,
M Lagarde
,
A Lalanne
,
A Lalieu
,
P Lannoy
,
J Lapchin
,
M Laprand
,
D Laude
,
R Leblanc
,
P Lecieux
,
S Lecleire
,
N Leclerc
,
C Le Couteulx
,
J Ledent
,
J Lefebvre
,
P Lefiliatre
,
C Le Goffic
,
C Legrand
,
A Le Grix
,
P Lelong
,
B Leluyer
,
C Lemaitre
,
C Lenaerts
,
G Lepeut
,
L Lepileur
,
A Leplat
,
E Lepoutre-Dujardin
,
H Leroi
,
M Leroy
,
P Le Roy
,
B Lesage
,
J Lesage
,
X Lesage
,
J Lesage
,
I Lescanne-Darchis
,
J Lescut
,
D Lescut
,
B Leurent
,
P Levy
,
M Lhermie
,
L Libier
,
A Lion
,
B Lisambert
,
I Loge
,
F Loire
,
J Loreau
,
S Louf
,
A Louvet
,
L Lubret
,
M Luciani
,
D Lucidarme
,
J Lugand
,
Eric N’guyen Khac
(12, 14, 13)
1
CHRU Lille -
Centre Hospitalier Régional Universitaire [CHU Lille]
2 INFINITE (Ex-Liric) - Institute for Translational Research in Inflammation - U 1286
3 ADEN - Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau
4 IRIB - Institute for Research and Innovation in Biomedicine
5 UNIROUEN - Université de Rouen Normandie
6 Service d'Hépato-Gastroentérologie [CHU Rouen]
7 METRICS - Evaluation des technologies de santé et des pratiques médicales - ULR 2694
8 MODAL - MOdel for Data Analysis and Learning
9 Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille]
10 CHU Reims - Hôpital universitaire Robert Debré [Reims]
11 PERITOX - Périnatalité et Risques Toxiques - UMR INERIS_I 1
12 CHU Amiens-Picardie
13 Registre EPIMAD
14 GRAP - Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 UPJV
2 INFINITE (Ex-Liric) - Institute for Translational Research in Inflammation - U 1286
3 ADEN - Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau
4 IRIB - Institute for Research and Innovation in Biomedicine
5 UNIROUEN - Université de Rouen Normandie
6 Service d'Hépato-Gastroentérologie [CHU Rouen]
7 METRICS - Evaluation des technologies de santé et des pratiques médicales - ULR 2694
8 MODAL - MOdel for Data Analysis and Learning
9 Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille]
10 CHU Reims - Hôpital universitaire Robert Debré [Reims]
11 PERITOX - Périnatalité et Risques Toxiques - UMR INERIS_I 1
12 CHU Amiens-Picardie
13 Registre EPIMAD
14 GRAP - Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 UPJV
Guillemette Marot
- Function : Author
- PersonId : 743200
- IdHAL : guillemette-marot
- ORCID : 0000-0002-7437-8239
- IdRef : 144465469
Jean-Pierre Hugot
- Function : Author
Fred Princen
- Function : Author
Mathurin Fumery
- Function : Author
- PersonId : 774088
- ORCID : 0000-0002-2337-2902
- IdRef : 170096289
A Baudet
- Function : Author
P Bayart
- Function : Author
B Bazin
- Function : Author
A Bebahani
- Function : Author
J Becqwort
- Function : Author
S Bellati
- Function : Author
V Benet
- Function : Author
H Benali
- Function : Author
C Benard
- Function : Author
C Benguigui
- Function : Author
E Ben Soussan
- Function : Author
A Bental
- Function : Author
I Berkelmans
- Function : Author
J Bernet
- Function : Author
K Bernou
- Function : Author
C Bernou-Dron
- Function : Author
P Bertot
- Function : Author
N Bertiaux-Vandaële
- Function : Author
V Bertrand
- Function : Author
E Billoud
- Function : Author
N Biron
- Function : Author
B Bismuth
- Function : Author
M Bleuet
- Function : Author
F Blondel
- Function : Author
V Blondin
- Function : Author
M Bobula
- Function : Author
P Bohon
- Function : Author
V Bondjemah
- Function : Author
E Boniface
- Function : Author
D Bonkovski
- Function : Author
P Bonnière
- Function : Author
E Bonvarlet
- Function : Author
P Bonvarlet
- Function : Author
A Boruchowicz
- Function : Author
R Bostvironnois
- Function : Author
M Boualit
- Function : Author
A Bouazza
- Function : Author
B Bouche
- Function : Author
C Boudaillez
- Function : Author
C Bourgeaux
- Function : Author
M Bourgeois
- Function : Author
A Bourguet
- Function : Author
A Bourienne
- Function : Author
H Boutaleb
- Function : Author
A Bouthors
- Function : Author
J Branche
- Function : Author
G Bray
- Function : Author
P Breban
- Function : Author
M Bridenne
- Function : Author
H Brihier
- Function : Author
L Bril
- Function : Author
V Brung-Lefebvre
- Function : Author
P Bulois
- Function : Author
P Burgiere
- Function : Author
J Butel
- Function : Author
J Canva
- Function : Author
V Canva-Delcambre
- Function : Author
J Capron
- Function : Author
F Cardot
- Function : Author
S Carette
- Function : Author
P Carpentier
- Function : Author
E Cartier
- Function : Author
J Cassar
- Function : Author
M Cassagnou
- Function : Author
J Castex
- Function : Author
P Catala
- Function : Author
S Cattan
- Function : Author
S Catteau
- Function : Author
B Caujolle
- Function : Author
G Cayron
- Function : Author
C Chandelier
- Function : Author
M Chantre
- Function : Author
J Charles
- Function : Author
T Charneau
- Function : Author
M Chavance-Thelu
- Function : Author
A Cheny
- Function : Author
D Chirita
- Function : Author
A Choteau
- Function : Author
J Claerbout
- Function : Author
P Clergue
- Function : Author
H Coevoet
- Function : Author
G Cohen
- Function : Author
R Collet
- Function : Author
M Colin
- Function : Author
J Colombel
- Function : Author
S Coopman
- Function : Author
L Cordiez
- Function : Author
J Corvisart
- Function : Author
A Cortot
- Function : Author
F Couttenier
- Function : Author
J Crinquette
- Function : Author
V Crombe
- Function : Author
I Dadamessi
- Function : Author
H Daoudi
- Function : Author
V Dapvril
- Function : Author
T Davion
- Function : Author
S Dautreme
- Function : Author
J Debas
- Function : Author
S Decoster
- Function : Author
N Degrave
- Function : Author
F Dehont
- Function : Author
C Delatre
- Function : Author
R Delcenserie
- Function : Author
D Delesalle
- Function : Author
O Delette
- Function : Author
T Delgrange
- Function : Author
L Delhoustal
- Function : Author
J Delmotte
- Function : Author
S Demmane
- Function : Author
G Deregnaucourt
- Function : Author
P Descombes
- Function : Author
J Desechalliers
- Function : Author
P Desmet
- Function : Author
P Desreumaux
- Function : Author
G Desseaux
- Function : Author
P Desurmont
- Function : Author
A Devienne
- Function : Author
E Devouge
- Function : Author
M Devred
- Function : Author
A Devroux
- Function : Author
A Dewailly
- Function : Author
S Dharancy
- Function : Author
A Di Fiore
- Function : Author
D Djedir
- Function : Author
R Djedir
- Function : Author
W Doleh
- Function : Author
M Dreher-Duwat
- Function : Author
R Dubois
- Function : Author
C Duburque
- Function : Author
P Ducatillon
- Function : Author
J Duclay
- Function : Author
B Ducrocq
- Function : Author
F Ducrot
- Function : Author
P Ducrotte
- Function : Author
A Dufilho
- Function : Author
C Duhamel
- Function : Author
D Dujardin
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C Dumant-Forest
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J Dupas
- Function : Author
F Dupont
- Function : Author
Y Duranton
- Function : Author
A Duriez
- Function : Author
N Duveau
- Function : Author
K El Achkar
- Function : Author
M El Farisi
- Function : Author
C Elie
- Function : Author
M Elie-Legrand
- Function : Author
A Elkhaki
- Function : Author
M Eoche
- Function : Author
E Essmaeel
- Function : Author
D Evrard
- Function : Author
J Evrard
- Function : Author
A Fatome
- Function : Author
B Filoche
- Function : Author
L Finet
- Function : Author
M Flahaut
- Function : Author
C Flamme
- Function : Author
D Foissey
- Function : Author
P Fournier
- Function : Author
M Foutrein-Comes
- Function : Author
P Foutrein
- Function : Author
D Fremond
- Function : Author
T Frere
- Function : Author
P Gallais
- Function : Author
C Gamblin
- Function : Author
S Ganga
- Function : Author
R Gerard
- Function : Author
G Geslin
- Function : Author
Y Gheyssens
- Function : Author
N Ghossini
- Function : Author
S Ghrib
- Function : Author
T Gilbert
- Function : Author
B Gillet
- Function : Author
D Godart
- Function : Author
P Godard
- Function : Author
J Godchaux
- Function : Author
R Godchaux
- Function : Author
G Goegebeur
- Function : Author
O Goria
- Function : Author
F Gottrand
- Function : Author
P Gower
- Function : Author
B Grandmaison
- Function : Author
M Groux
- Function : Author
C Guedon
- Function : Author
L Guerbeau
- Function : Author
M Gueroult-Dero
- Function : Author
J Guillard
- Function : Author
L Guillem
- Function : Author
F Guillemot
- Function : Author
D Guimberd
- Function : Author
B Haddouche
- Function : Author
S Hakim
- Function : Author
D Hanon
- Function : Author
V Hautefeuille
- Function : Author
P Heckestweiller
- Function : Author
G Hecquet
- Function : Author
J Hedde
- Function : Author
H Hellal
- Function : Author
P Henneresse
- Function : Author
B Heyman
- Function : Author
M Heraud
- Function : Author
S Herve
- Function : Author
P Hochain
- Function : Author
L Houssin-Bailly
- Function : Author
P Houcke
- Function : Author
B Huguenin
- Function : Author
S Iobagiu
- Function : Author
S Istanboli
- Function : Author
A Ivanovic
- Function : Author
I Iwanicki-Caron
- Function : Author
E Janicki
- Function : Author
M Jarry
- Function : Author
J Jeu
- Function : Author
J Joly
- Function : Author
C Jonas
- Function : Author
A Jouvenet
- Function : Author
F Katherin
- Function : Author
A Kerleveo
- Function : Author
A Khachfe
- Function : Author
A Kiriakos
- Function : Author
J Kiriakos
- Function : Author
O Klein
- Function : Author
M Kohut
- Function : Author
R Kornhauser
- Function : Author
D Koutsomanis
- Function : Author
J Laberenne
- Function : Author
E Lacotte
- Function : Author
G Laffineur
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M Lagarde
- Function : Author
A Lalanne
- Function : Author
A Lalieu
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P Lannoy
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J Lapchin
- Function : Author
M Laprand
- Function : Author
D Laude
- Function : Author
R Leblanc
- Function : Author
P Lecieux
- Function : Author
S Lecleire
- Function : Author
N Leclerc
- Function : Author
C Le Couteulx
- Function : Author
J Ledent
- Function : Author
J Lefebvre
- Function : Author
P Lefiliatre
- Function : Author
C Le Goffic
- Function : Author
C Legrand
- Function : Author
A Le Grix
- Function : Author
P Lelong
- Function : Author
B Leluyer
- Function : Author
C Lemaitre
- Function : Author
C Lenaerts
- Function : Author
G Lepeut
- Function : Author
L Lepileur
- Function : Author
A Leplat
- Function : Author
E Lepoutre-Dujardin
- Function : Author
H Leroi
- Function : Author
M Leroy
- Function : Author
P Le Roy
- Function : Author
B Lesage
- Function : Author
J Lesage
- Function : Author
X Lesage
- Function : Author
J Lesage
- Function : Author
I Lescanne-Darchis
- Function : Author
J Lescut
- Function : Author
D Lescut
- Function : Author
B Leurent
- Function : Author
P Levy
- Function : Author
M Lhermie
- Function : Author
L Libier
- Function : Author
A Lion
- Function : Author
B Lisambert
- Function : Author
I Loge
- Function : Author
F Loire
- Function : Author
J Loreau
- Function : Author
S Louf
- Function : Author
A Louvet
- Function : Author
L Lubret
- Function : Author
M Luciani
- Function : Author
D Lucidarme
- Function : Author
J Lugand
- Function : Author
Eric N’guyen Khac
- Function : Contributor
- PersonId : 863504
- ORCID : 0000-0001-8672-4146
- IdRef : 081127634
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.