Researchers have developed and validated an integrative risk score that can predict the risk of developing Crohn’s disease in people with a first-degree relative living with the condition. The risk score is an important step toward the goal of identifying and preventing disease onset in at-risk populations, according to the investigators.
“Increasing research has identified that the earlier we intervene and treat Crohn’s disease, the better the outcomes,” said Ryan Ungaro, MD, MS, the director of clinical research in the Division of Gastroenterology at Icahn School of Medicine at Mount Sinai, in New York City, who was not involved in the research. “In addition, we now know that Crohn’s disease is preceded by a prolonged preclinical phase, creating the potential opportunity to prevent or delay the onset of disease.”
The study followed 2,619 healthy participants in North America and Israel who had a first-degree relative with Crohn’s disease Gastroenterology (2024 Aug 30. doi:10.1053/j.gastro.2024.08.021). During a median follow-up duration of 6.8 years, 61 of these participants—or 2.3%—developed Crohn’s disease.
To develop the integrative risk score model, called the Crohn’s Colitis Canada Genetic, Environmental, Microbial (GEM) integrative risk score, researchers used all available demographic characteristics, physiologic biomarkers and fecal microbiome data from the study participants.
According to the researchers, the GEM integrative risk score resulted in a predictive performance of 0.951 (95% CI, 0.925-0.976) in the North American training cohort and a concordance index of 0.789 (95% CI, 0.713-0.865) in the pooled testing cohort.
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“We believe the integrative model showed the potential to risk-stratify high-risk individuals among healthy [first-degree relatives], which is the first step toward designing a primary prevention trial in Crohn’s disease,” the researchers, led by Sun-Ho Lee, MD, PhD, an assistant professor and clinical scientist in the Division of Gastroenterology and Hepatology at the University of Toronto, wrote. “Further research is warranted to develop a model that is clinically applicable. We also need to validate and calibrate the findings in external cohorts (given the possible model instability due to a small number of events) and to determine to what extent asymptomatic persons identified to be at high risk of Crohn’s disease will be willing to undertake interventional therapy.”
Dr. Ungaro, who is part of a team that recently published a study identifying a biomarker that may predict Crohn’s years in advance, pointed to a limitation of the risk score study, “the reliance on stool markers, which may be more challenging to collect.” However, he said the study “brings us closer to identifying people at higher risk of developing Crohn’s disease, who could then be enrolled in closer monitoring or disease prevention trials.”
—Ashley Welch
Dr. Ungaro reported financial relationships with AbbVie, BMS, Celltrion, Inotrem, Janssen, Lilly, Pfizer, Roivant and Takeda.
This article is from the December 2024 print issue.