Study Identifies Gene Signatures for Crohn's Disease in Children

March 2, 2017
Study Identifies Gene Signatures for Crohn's Disease in Children
Source: © Sebastian Kaulitzki/Fotolia

Children with newly diagnosed Crohn's disease have biological signatures that can predict if they will develop disease-related complications requiring major surgery within three to five years—offering a new avenue to treating the disease through precision medicine, according to a study published today.

The finding was among results of the Crohn’s & Colitis Foundation’s “RISK Stratification” study, designed to identify measurable indicators of stricturing and penetrating disease, the two most common complications in pediatric Crohn's disease that require surgery. The multicenter research initiative consisted of 28 institutions—25 from the U.S., the rest from Canada.

The study enrolled 1,800 patients, including a cohort of 1,112 children with Crohn’s disease who were enrolled at diagnosis. Researchers focused on 913 of those children, who not only had Crohn’s disease but were complication-free following 90 days after diagnosis.

Patients underwent clinical, demographic, and biological sample collection every six months for three years with, continuing follow up for five years.

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

“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,” Ted Denson, M.D., of Cincinnati Children's Hospital, co-principal investigator and one of three lead authors of the study, said in a statement.

Added Subra Kugathasan, M.D., of Emory University, principal investigator and a lead author: “25% of patients with Crohn's disease account for 80% of complications, hospitalizations, surgery, and health care costs. The aim of RISK is to preemptively identify those 25% of patients at diagnosis.”

Drs. Kugathasan and Denson were joined as lead authors by Thomas Walters, MBBS, of the Hospital for Sick Children (SickKids) in Toronto.

The RISK study also found that patients who receive early anti- tumor necrosis factor alpha (TNFα) 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.

The Foundation said the study data supported the utility of risk stratification of pediatric Crohn's disease patients at diagnosis, and may guide early tailored use of anti-TNFα therapy. The data also highlighted the unmet medical need of new treatment options for children likely to develop strictures.

“These discoveries are great steps toward precision medicine in the treatment of pediatric Crohn's disease,” stated Andrés Hurtado-Lorenzo, PhD, the foundation’s director of translational research. “In the coming years, we plan to translate these findings into a risk diagnostic tool that could use these biological signatures as biomarkers to predict risk of complications and to help clinicians make therapeutic decisions at diagnosis.”

The study, “Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study,” was published today in The Lancet.

The study and related research reflects nearly 10 years and more than $10 million of investment, according to the Foundation, which said the RISK study was the largest new-onset study completed on pediatric Crohn's disease patients.

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