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Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study. Lancet 2017 04 29;389(10080):1710-1718

Date

03/06/2017

Pubmed ID

28259484

Pubmed Central ID

PMC5719489

DOI

10.1016/S0140-6736(17)30317-3

Scopus ID

2-s2.0-85014105950   253 Citations

Abstract

BACKGROUND: Stricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohn's disease. Validated models to predict risk for complications are not available, and the effect of treatment on risk is unknown.

METHODS: We did a prospective inception cohort study of paediatric patients with newly diagnosed Crohn's disease at 28 sites in the USA and Canada. Genotypes, antimicrobial serologies, ileal gene expression, and ileal, rectal, and faecal microbiota were assessed. A competing-risk model for disease complications was derived and validated in independent groups. Propensity-score matching tested the effect of anti-tumour necrosis factor α (TNFα) therapy exposure within 90 days of diagnosis on complication risk.

FINDINGS: Between Nov 1, 2008, and June 30, 2012, we enrolled 913 patients, 78 (9%) of whom experienced Crohn's disease complications. The validated competing-risk model included age, race, disease location, and antimicrobial serologies and provided a sensitivity of 66% (95% CI 51-82) and specificity of 63% (55-71), with a negative predictive value of 95% (94-97). Patients who received early anti-TNFα therapy were less likely to have penetrating complications (hazard ratio [HR] 0·30, 95% CI 0·10-0·89; p=0·0296) but not stricturing complication (1·13, 0·51-2·51; 0·76) than were those who did not receive early anti-TNFα therapy. Ruminococcus was implicated in stricturing complications and Veillonella in penetrating complications. Ileal genes controlling extracellular matrix production were upregulated at diagnosis, and this gene signature was associated with stricturing in the risk model (HR 1·70, 95% CI 1·12-2·57; p=0·0120). When this gene signature was included, the model's specificity improved to 71%.

INTERPRETATION: Our findings support the usefulness of risk stratification of paediatric patients with Crohn's disease at diagnosis, and selection of anti-TNFα therapy.

FUNDING: Crohn's and Colitis Foundation of America, Cincinnati Children's Hospital Research Foundation Digestive Health Center.

Author List

Kugathasan S, Denson LA, Walters TD, Kim MO, Marigorta UM, Schirmer M, Mondal K, Liu C, Griffiths A, Noe JD, Crandall WV, Snapper S, Rabizadeh S, Rosh JR, Shapiro JM, Guthery S, Mack DR, Kellermayer R, Kappelman MD, Steiner S, Moulton DE, Keljo D, Cohen S, Oliva-Hemker M, Heyman MB, Otley AR, Baker SS, Evans JS, Kirschner BS, Patel AS, Ziring D, Trapnell BC, Sylvester FA, Stephens MC, Baldassano RN, Markowitz JF, Cho J, Xavier RJ, Huttenhower C, Aronow BJ, Gibson G, Hyams JS, Dubinsky MC

Author

Joshua D. Noe MD Associate Dean, Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adalimumab
Adolescent
Anti-Inflammatory Agents, Non-Steroidal
Child
Cohort Studies
Crohn Disease
Disease Progression
Female
Gastrointestinal Microbiome
Humans
Infliximab
Intestinal Obstruction
Male
Prognosis
Propensity Score
Prospective Studies
Risk Assessment
Severity of Illness Index
Tumor Necrosis Factor-alpha