Clinical predictors at diagnosis of disabling pediatric Crohn's disease

Background: Identification of children with Crohn's disease (CD) at high risk of disabling disease would be invaluable in guiding initial therapy. Our study aimed to identify predictors at diagnosis of a subsequent disabling course in a population‐based cohort of patients with pediatric‐onset CD. Methods: Among 537 patients with pediatric CD diagnosed at <17 years of age, 309 (57%) with 5‐year follow‐up were included. Clinical and demographic factors associated with subsequent disabling CD were studied. Three definitions of disabling CD were used: Saint‐Antoine and Liège Hospitals' definitions and a new pediatric definition based on the presence at maximal follow‐up of: 1) growth delay defined by body mass index (BMI), weight or height lower than −2 SD Z score; and 2) at least one intestinal resection or two anal interventions. Predictors were determined using multivariate analyses and their accuracy using the kappa method considering a relevant value ≥0.6. Results: According to the Saint‐Antoine definition, the rate of disabling CD was 77% and predictors were complicated behavior and L1 location. According to the Liège definition, the rate was 37% and predictors included behavior, upper gastrointestinal disease, and extraintestinal manifestations. According to the pediatric definition, the rate of disabling CD was 15%, and predictors included complicated behavior, age <14, and growth delay at diagnosis. Kappa values for each combination of predictors were, respectively, 0.2, 0.3, and 0.2 and were nonrelevant. Conclusions: Clinical parameters at diagnosis are insufficient to predict a disabling course of pediatric CD. More complex models including serological and genetic biomarkers should be tested. (Inflamm Bowel Dis 2012;)

[1]  B. Abraham,et al.  Disability in inflammatory bowel disease. , 2012, Gastroenterology clinics of North America.

[2]  F. Vasseur,et al.  Long‐term outcome of treatment with infliximab in pediatric‐onset Crohn's disease: A population‐based study , 2011, Inflammatory bowel diseases.

[3]  David C Wilson,et al.  Pediatric modification of the Montreal classification for inflammatory bowel disease: The Paris classification , 2011, Inflammatory bowel diseases.

[4]  J. Salleron,et al.  Early Surgery is Not Associated With Poor Prognosis in Pediatric Crohn's Disease: A Population-Based Study , 2011 .

[5]  A. Cieza,et al.  Disability in Inflammatory Bowel Disease (IBD): Developing Icf Core Sets for Patients With IBD Based on the WHO International Classification of Functioning, Disability and Health , 2011 .

[6]  M. Dubinsky,et al.  Real‐time tool to display the predicted disease course and treatment response for children with Crohn's disease , 2011, Inflammatory bowel diseases.

[7]  H. Tilg,et al.  Development of the Crohn's disease digestive damage score, the Lémann score , 2010, Inflammatory bowel diseases.

[8]  A. Zinsmeister,et al.  Risk factors associated with progression to intestinal complications of Crohn's disease in a population-based cohort. , 2010, Gastroenterology.

[9]  F. Vasseur,et al.  Nutritional Status and Growth in Pediatric Crohn's Disease: A Population-Based Study , 2010, The American Journal of Gastroenterology.

[10]  J. Schölmerich,et al.  Increased Response and Remission Rates in Short-Duration Crohn's Disease With Subcutaneous Certolizumab Pegol: An Analysis of PRECiSE 2 Randomized Maintenance Trial Data , 2010, The American Journal of Gastroenterology.

[11]  P. Rutgeerts,et al.  Infliximab, azathioprine, or combination therapy for Crohn's disease. , 2010, The New England journal of medicine.

[12]  L. Peyrin-Biroulet,et al.  The Natural History of Adult Crohn's Disease in Population-Based Cohorts , 2010, The American Journal of Gastroenterology.

[13]  P. Rutgeerts,et al.  Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. , 2010, Gastroenterology.

[14]  Andre Franke,et al.  Genetic risk profiling and prediction of disease course in Crohn's disease patients. , 2009, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[15]  P. Lakatos,et al.  Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn's disease. , 2009, World journal of gastroenterology.

[16]  S. Necozione,et al.  Clinical course of Crohn's disease first diagnosed at surgery for acute abdomen. , 2009, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[17]  P. Rutgeerts,et al.  Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease: results from the CHARM study. , 2008, Gastroenterology.

[18]  K. Van Steen,et al.  Long-term outcome of treatment with infliximab in 614 patients with Crohn’s disease: results from a single-centre cohort , 2008, Gut.

[19]  S. Targan,et al.  Increased immune reactivity predicts aggressive complicating Crohn's disease in children. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[20]  Julia Salleron,et al.  Natural history of pediatric Crohn's disease: a population-based cohort study. , 2008, Gastroenterology.

[21]  C. Wijmenga,et al.  Molecular prediction of disease risk and severity in a large Dutch Crohn’s disease cohort , 2008, Gut.

[22]  A. Griffiths,et al.  Effect of early immunomodulator use in moderate to severe pediatric Crohn disease , 2008, Inflammatory bowel diseases.

[23]  T. Molnár,et al.  New Serological Markers for Inflammatory Bowel Disease Are Associated With Earlier Age at Onset, Complicated Disease Behavior, Risk for Surgery, and NOD2/CARD15 Genotype in a Hungarian IBD Cohort , 2008, The American Journal of Gastroenterology.

[24]  M. Vos,et al.  Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial , 2008, The Lancet.

[25]  J. Belaiche,et al.  Predictors of severe Crohn's disease , 2008, Scandinavian journal of gastroenterology.

[26]  M. Vatn,et al.  Clinical course in Crohn's disease: results of a Norwegian population-based ten-year follow-up study. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[27]  K. Van Steen,et al.  New serological markers in inflammatory bowel disease are associated with complicated disease behaviour , 2007, Gut.

[28]  A. Griffiths,et al.  Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. , 2007, Gastroenterology.

[29]  S. Schreiber,et al.  P178 Early Crohn's Disease Shows High Levels of Remission to Therapy with Adalimumab: Sub-Analysis of Charm , 2007 .

[30]  A. Griffiths,et al.  Corticosteroid therapy in the age of infliximab: acute and 1-year outcomes in newly diagnosed children with Crohn's disease. , 2006, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[31]  S. Dorn Predictors of Crohn's disease. , 2006, Gastroenterology.

[32]  J. Satsangi,et al.  The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications , 2006, Gut.

[33]  E. Seidman,et al.  Utility of Serological Markers in Predicting the Early Occurrence of Complications and Surgery in Pediatric Crohn's Disease Patients , 2006, The American Journal of Gastroenterology.

[34]  K. Herrmann,et al.  Homozygosity for the CARD15 frameshift mutation 1007fs is predictive of early onset of Crohn's disease with ileal stenosis, entero-enteral fistulas, and frequent need for surgical intervention with high risk of re-stenosis , 2006, Scandinavian journal of gastroenterology.

[35]  S. Vermeire,et al.  Phenotype at diagnosis predicts recurrence rates in Crohn’s disease , 2005, Gut.

[36]  P. Rutgeerts,et al.  Association of organic cation transporter risk haplotype with perianal penetrating Crohn's disease but not with susceptibility to IBD. , 2005, Gastroenterology.

[37]  A. Lacy,et al.  Crohn's Disease Patients Carrying Nod2/CARD15 Gene Variants Have an Increased and Early Need for First Surgery due to Stricturing Disease and Higher Rate of Surgical Recurrence , 2005, Annals of surgery.

[38]  M. Bala,et al.  Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn's disease. , 2005, Gastroenterology.

[39]  A. Andriulli,et al.  Variants of CARD15 are Associated with an Aggressive Clinical Course of Crohn's Disease—An IG-IBD Study , 2005, The American Journal of Gastroenterology.

[40]  H. Drummond,et al.  Sero-Reactivity to Microbial Components in Crohn's Disease Is Associated with Disease Severity and Progression, but not NOD2/CARD15 Genotype , 2004, The American Journal of Gastroenterology.

[41]  J. Ioannidis,et al.  Differential Effects of NOD2 Variants on Crohn's Disease Risk and Phenotype in Diverse Populations: A Metaanalysis , 2004, The American Journal of Gastroenterology.

[42]  D. M. van der Heijde,et al.  Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. , 2004, Arthritis and rheumatism.

[43]  É. Lerebours,et al.  Opposite evolution in incidence of Crohn’s disease and ulcerative colitis in Northern France (1988–1999) , 2004, Gut.

[44]  P. Rutgeerts,et al.  Infliximab maintenance therapy for fistulizing Crohn's disease. , 2004, The New England journal of medicine.

[45]  Samir A. Shah,et al.  Risk of early surgery for Crohn's disease: implications for early treatment strategies , 2003, American Journal of Gastroenterology.

[46]  F. Carbonnel,et al.  Long-Term Evolution of Disease Behavior of Crohn's Disease , 2002, Inflammatory bowel diseases.

[47]  Richard W. Martin,et al.  Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. , 2002, Arthritis and rheumatism.

[48]  S. Hanauer,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[49]  R. Jian,et al.  Long term outcome of patients with active Crohn's disease exhibiting extensive and deep ulcerations at colonoscopy , 2002, American Journal of Gastroenterology.

[50]  J. Belaiche,et al.  Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease , 2001, Gut.

[51]  F. T. Veloso,et al.  Clinical Outcome of Crohn's Disease: Analysis According to the Vienna Classification and Clinical Activity , 2001, Inflammatory bowel diseases.

[52]  Richard W. Martin,et al.  A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. , 2000, The New England journal of medicine.

[53]  P. Rutgeerts,et al.  Endoscopic and histologic healing of Crohn's (ileo-) colitis with azathioprine. , 1999, Gastrointestinal endoscopy.

[54]  J. Colombel,et al.  Incidence of inflammatory bowel disease in northern France (1988-1990). , 1994, Gut.

[55]  J. R. Landis,et al.  The measurement of observer agreement for categorical data. , 1977, Biometrics.

[56]  G. Lichtenstein New serological markers in inflammatory bowel disease are associated with complicated disease behaviour , 2008 .

[57]  P. Rutgeerts,et al.  Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. , 2007, Gastroenterology.

[58]  F. Breedveld,et al.  The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. , 2006, Arthritis and rheumatism.

[59]  P. Rutgeerts,et al.  Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease. , 2006, Gastrointestinal endoscopy.

[60]  S. Targan,et al.  Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease. , 2002, Gastroenterology.