TY - JOUR
T1 - Prediction of complicated disease course for children newly diagnosed with Crohn's disease
T2 - a multicentre inception cohort study
AU - Kugathasan, Subra
AU - Denson, Lee A.
AU - Walters, Thomas D.
AU - Kim, Mi Ok
AU - Marigorta, Urko M.
AU - Schirmer, Melanie
AU - Mondal, Kajari
AU - Liu, Chunyan
AU - Griffiths, Anne
AU - Noe, Joshua D.
AU - Crandall, Wallace V.
AU - Snapper, Scott
AU - Rabizadeh, Shervin
AU - Rosh, Joel R.
AU - Shapiro, Jason M.
AU - Guthery, Stephen
AU - Mack, David R.
AU - Kellermayer, Richard
AU - Kappelman, Michael D.
AU - Steiner, Steven
AU - Moulton, Dedrick E.
AU - Keljo, David
AU - Cohen, Stanley
AU - Oliva-Hemker, Maria
AU - Heyman, Melvin B.
AU - Otley, Anthony R.
AU - Baker, Susan S.
AU - Evans, Jonathan S.
AU - Kirschner, Barbara S.
AU - Patel, Ashish S.
AU - Ziring, David
AU - Trapnell, Bruce C.
AU - Sylvester, Francisco A.
AU - Stephens, Michael C.
AU - Baldassano, Robert N.
AU - Markowitz, James F.
AU - Cho, Judy
AU - Xavier, Ramnik J.
AU - Huttenhower, Curtis
AU - Aronow, Bruce J.
AU - Gibson, Greg
AU - Hyams, Jeffrey S.
AU - Dubinsky, Marla C.
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/4/29
Y1 - 2017/4/29
N2 - 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.
AB - 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.
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U2 - 10.1016/S0140-6736(17)30317-3
DO - 10.1016/S0140-6736(17)30317-3
M3 - Article
C2 - 28259484
AN - SCOPUS:85014105950
SN - 0140-6736
VL - 389
SP - 1710
EP - 1718
JO - The Lancet
JF - The Lancet
IS - 10080
ER -