A subset of patients with Crohn’s disease develops progressive complications such as narrowing of the gastrointestinal tract (stricturing) and the formation of fistulas (penetration). A validated model to predict the risk of such complications has now been proposed in a new study in The Lancet. This the first report to provide risk stratification, and could be useful in making personalized treatment decisions.
Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract, characterized by abdominal cramps, diarrhea, fatigue, and weight loss. A subgroup of patients with an initial diagnosis of Crohn’s disease eventually develops complications such as the development of strictures (tract narrowing) and/or fistulas (abnormal connection between two spaces). Not everyone has such complications, and a validated model for predicting the risk is unknown. Furthermore, there is no cure for Crohn’s disease, and most medications are aimed at symptom management/control of disease progression. A commonly used treatment approach involves administering patients with a biologic called anti-TNF alpha. The drug acts to decrease inflammation in the gut, resulting in remission. However, certain patients still develop complications in spite of an early start of the treatment.
A new study published in The Lancet, involving researchers in the United States and Canada, developed the first model of risk prediction in a pediatric population newly diagnosed with Crohn’s disease. The study involved 913 children aged 18 and under, presenting with a non-penetrating and non-stricturing disease phenotype. A subset of these patients also received anti-TNF-alpha therapy. Researchers obtained blood, stool and colonic mucosal samples from these patients, when available. Global gene expression profiling was performed on RNA isolated from biopsies of the small intestine, and microbial profiling was done on samples collected from the small intestine and rectum.
Gene expression profiling revealed that in patients who ultimately developed stricturing complications, there was a pronounced increase in the expression of genes involved in the formation of a fibrotic extracellular matrix. The study also found that early treatment with anti-TNF-alpha therapy decreased incidences of internal penetrating, but not rates of stricturing. The researchers, therefore, propose that gene expression profiling could be used to identify patients with potential stricturing complications in the future, and guide more efficient enrollment into trials of anti-fibrotic therapies.
The other risk factors for disease complications include older age, African American race, and the presence of antibodies to certain bacteria/bacterial proteins such as anti-Saccharomyces cerevisiae (ASCA) and anti-flagellin (cBir1) in the blood. The study also identified 14 microbial genera associated with pediatric Crohn’s disease.
Overall, the results hold much promise, and if validated in a future clinical study, the risk prediction model could be used to develop more personalized approaches towards the effective management of Crohn’s disease complications.
Written By: Debapriya Dutta, PhD