title: A validated web-based tool to display individualised Crohn's disease predicted outcomes based on clinical, serologic and genetic variables.
abstract: BACKGROUND
  Early treatment for Crohn's disease (CD) with immunomodulators and/or anti-TNF agents improves outcomes in comparison to a slower 'step up' algorithm. However, there remains a limited ability to identify those who would benefit most from early intensive therapy.
  
  
  OBJECTIVE
  To develop a validated, individualised, web-based tool for patients and clinicians to visualise individualised risks for developing Crohn's disease complications.
  
  
  METHODS
  A well-characterised cohort of adult patients with CD was analysed. Available data included: demographics; clinical characteristics; serologic immune responses; NOD2 status; time from diagnosis to complication; and medication exposure. Cox proportional analyses were performed to model the probability of developing a CD complication over time. The Cox model was validated externally in two independent CD cohorts. Using system dynamics analysis (SDA), these results were transformed into a simple graphical web-based display to show patients their individualised probability of developing a complication over a 3-year period.
  
  
  RESULTS
  Two hundered and forty three CD patients were included in the final model of which 142 experienced a complication. Significant variables in the multivariate Cox model included small bowel disease (HR 2.12, CI 1.05-4.29), left colonic disease (HR 0.73, CI 0.49-1.09), perianal disease (HR 4.12, CI 1.01-16.88), ASCA (HR 1.35, CI 1.16-1.58), Cbir (HR 1.29, CI 1.07-1.55), ANCA (HR 0.77, CI 0.62-0.95), and the NOD2 frameshift mutation/SNP13 (HR 2.13, CI 1.33-3.40). The Harrell's C (concordance index for predictive accuracy of the model) = 0.73. When applied to the two external validation cohorts (adult n = 109, pediatric n = 392), the concordance index was 0.73 and 0.75, respectively, for adult and pediatric patients.
  
  
  CONCLUSIONS
  A validated, web-based tool has been developed to display an individualised predicted outcome for adult patients with Crohn's disease based on clinical, serologic and genetic variables. This tool can be used to help providers and patients make personalised decisions about treatment options.
authors.affiliation: Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.|Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Siegel
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Horton
authors.affiliation: Siegel Environmental Dynamics, Hanover, NH, USA.|Climate Interactive, Washington, DC, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Siegel
authors.affiliation: Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.|Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Thompson
authors.affiliation: Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: T
authors.initials: T
authors.lastname: Mackenzie
authors.affiliation: Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Stewart
authors.affiliation: Climate Interactive, Washington, DC, USA.
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authors.initials: PW
authors.lastname: Rice
authors.affiliation: Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Stempak
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dezfoli
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Haritunians
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Levy
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Baek
authors.affiliation: Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Milgrom
authors.affiliation: Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.|Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Dulai
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Targan
authors.affiliation: Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: M S
authors.initials: MS
authors.lastname: Silverberg
authors.affiliation: Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Dubinsky
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
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authors.initials: DP
authors.lastname: McGovern
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D020407:Internet; D008297:Male; D011446:Prospective Studies; D012189:Retrospective Studies; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha