C A Siegel1,2, H Horton3, L S Siegel4,5, K D Thompson1,2, T Mackenzie2, S K Stewart1, P W Rice5, J M Stempak6, S Dezfoli3, T Haritunians3, A Levy3, M Baek3, R Milgrom6, P S Dulai1,2, S R Targan3, M S Silverberg6, M C Dubinsky7, D P McGovern3. 1. Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. 2. Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. 3. F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 4. Siegel Environmental Dynamics, Hanover, NH, USA. 5. Climate Interactive, Washington, DC, USA. 6. Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. 7. Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
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. AIM: 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.
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. AIM: 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 CDpatients 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: Parambir S Dulai; Brigid S Boland; Siddharth Singh; Khadija Chaudrey; Jenna L Koliani-Pace; Gursimran Kochhar; Malav P Parikh; Eugenia Shmidt; Justin Hartke; Prianka Chilukuri; Joseph Meserve; Diana Whitehead; Robert Hirten; Adam C Winters; Leah G Katta; Farhad Peerani; Neeraj Narula; Keith Sultan; Arun Swaminath; Matthew Bohm; Dana Lukin; David Hudesman; John T Chang; Jesus Rivera-Nieves; Vipul Jairath; G Y Zou; Brian G Feagan; Bo Shen; Corey A Siegel; Edward V Loftus; Sunanda Kane; Bruce E Sands; Jean-Frederic Colombel; William J Sandborn; Karen Lasch; Charlie Cao Journal: Gastroenterology Date: 2018-05-30 Impact factor: 22.682
Authors: Christopher Ma; Carla Ascoytia; Kelly P McCarrier; Mona Martin; Brian G Feagan; Vipul Jairath Journal: Dig Dis Sci Date: 2018-06-29 Impact factor: 3.199
Authors: Mirna Šimurina; Noortje de Haan; Frano Vučković; Nicholas A Kennedy; Jerko Štambuk; David Falck; Irena Trbojević-Akmačić; Florent Clerc; Genadij Razdorov; Anna Khon; Anna Latiano; Renata D'Incà; Silvio Danese; Stephan Targan; Carol Landers; Marla Dubinsky; Dermot P B McGovern; Vito Annese; Manfred Wuhrer; Gordan Lauc Journal: Gastroenterology Date: 2018-01-06 Impact factor: 22.682