Ling-shiang (Felix) Chuang

5/9/2017

The complications of Crohn’s Disease (CD) such as fistulas or strictures are some of the main reasons that require patients to undergo surgery. A fistula is an abnormal channel connecting the intestine or colon to another internal organ, and strictures are narrowings in the intestine which can make it difficult for food matter to pass through. It has been hypothesized that early recognition and prompt treatment are the key to reduce complications. Drs. Subra Kugathasan, Judy Cho and Marla Dubinsky tested this hypothesis with RNA sequencing and clinical data from pediatric CD patients and showed that early treatment of anti-TNFα reduced the formation of fistulas but not strictures. This work has been published in the high impact journal The Lancet.

The new discovery started with Crohn’s and Colitis Foundation’s “RISK Stratification” study, the largest newly onset study completed on pediatric Crohn’s disease patients. A total cohort of 1,112 CD children enrolled upon diagnosis, of which 913 were included in the published study. Researchers used intestinal gene expression levels to identify risk factor genes and identified distinct biological gene expression signatures at baseline that could distinguish children who will develop strictures form those who develop fistulas or strictures. In combination with clinical data, they showed that patients who received early anti-TNFα therapy were less likely to have fistulas (p=0.0296) but not strictures (p= 0.76) than those who did not receive early anti-TNFα therapy. This research sheds light on building predictors of complications and treatment outcomes at time of diagnosis using genetic signatures and clinical variables.