• Profile
Close

RISK study reveals new precision medicine approach to Crohn's and colitis

Emory's Woodruff Health Sciences Center News Mar 08, 2017

Researchers have successfully identified biological signatures in pediatric patients with newly diagnosed Crohn's disease (CD) capable of predicting whether a child will develop disease–related complications requiring major surgery within three to five years. The results of this research, "Prediction of complicated disease course for children newly diagnosed with Crohn's disease: A multicentre inception cohort study," were published in The Lancet journal.

This groundbreaking work is the result of the Crohn's & Colitis Foundation's "RISK Stratification" study, the largest new–onset study completed on pediatric Crohn's disease patients. It is a multicenter research initiative that consists of 25 U.S. institutions and three from Canada and a cohort of 1,112 CD children enrolled at diagnosis, of which 913 were included in the published study. Of the 28 research sites, four are located in Atlanta – Emory University, Georgia Institute of Technology, Children's Healthcare of Atlanta, and the Children's Center for Digestive Health Care. The goal of this research was to identify measurable indicators of the two most common complications in pediatric Crohn's disease that require surgery – stricturing and penetrating disease.

Stricturing, also referred to as fibrostenosis, is characterized by a build–up of fibrotic scar tissue which leads to thickening of the intestinal wall and narrowing of the intestinal passage. Penetrating disease is the result of sustained inflammation that spreads beyond the intestinal wall resulting in the creation of fistulas, abnormal connections between the intestine and other organs.

Penetrating complications can also lead to the formation of abscesses at the sites of fistulas.

"Twenty five percent of patients with Crohn's disease account for 80 percent of complications, hospitalizations, surgery, and health care costs. The aim of RISK is to preemptively identify those 25 percent of patients at diagnosis," Subra Kugathasan, MD, Emory University, principal investigator and lead author of the paper. "Through the study of baseline gene expression, immune reactivity, and intestinal bacteria, we have identified distinct biological signatures capable of predicting stricturing and penetrating disease, at diagnosis. After analyzing millions of biological and clinical data points, RISK has generated a composite risk stratification model."

RISK study researchers looked at intestinal gene expression levels to identify risk factor genes whose levels are altered at enrollment, and identified distinct biological gene expression signatures at baseline that could distinguish children who will develop strictures form those who develop fistulas or abscesses, without the confounding effects of treatment on gene expression.

"Importantly, the functional nature of these genetic signatures is consistent with the clinical presentation of the complications," said Ted Denson, MD, Cincinnati Children's Hospital, co–principal investigator and lead author of the paper. "This means that while patients who develop fibrostenosis exhibit, at diagnosis, increased levels of several genes involved in the fibrosis process, patients who develop penetrating disease have increased levels of genes involved in the inflammatory response."

In addition to providing predictive biological signatures for development of complications, the RISK study also found that patients who receive early anti–TNF biologic treatment, within three months of diagnosis, were less likely to develop penetrating complications. However, patients with stricturing complications were poorly responsive to early intervention with biologics. These data support the utility of risk stratification of pediatric Crohn's disease patients at diagnosis, and may guide early tailored use of anti–TNF therapy.
Go to Original
Only Doctors with an M3 India account can read this article. Sign up for free or login with your existing account.
4 reasons why Doctors love M3 India
  • Exclusive Write-ups & Webinars by KOLs

  • Nonloggedininfinity icon
    Daily Quiz by specialty
  • Nonloggedinlock icon
    Paid Market Research Surveys
  • Case discussions, News & Journals' summaries
Sign-up / Log In
x
M3 app logo
Choose easy access to M3 India from your mobile!


M3 instruc arrow
Add M3 India to your Home screen
Tap  Chrome menu  and select "Add to Home screen" to pin the M3 India App to your Home screen
Okay