Series of Studies Identifies Predictive Tools for Crohn Disease

In a series of 4 studies published in Gastroenterology, researchers described the identification of predictive tools and a new understanding of environmental factors that trigger inflammatory bowel disease (IBD).

“Early identification of individuals [with a] high risk for disease development could allow for close monitoring and interventions to delay, attenuate, or even halt disease initiation. This is highly relevant as week to predict and prevent IBD, which continues to sharply increase in numbers across the globe,” said Jean-Frederic Colombel, MD, professor of Gastroenterology at the Icahn School of Medicine at Mount Sinai, in a press release. “In the absence of a cure, our clinical strategy will center on aggressive and innovative mechanisms to predict and prevent the disease.”

The series of studies provide 4 unique windows into IBD through prevention, according to the authors. They include the prevention of progression of early Crohn disease, predicting Crohn disease 5 years before first symptoms, the first study to evaluate association of metal exposure and IBD, the study of Ashkenazi Jewish families suggesting an environmental link.

Prevention of Progression of Early Crohn Disease

The Effect of Tight Control Management on Crohn Disease (CALM) study, a large, 31-site analysis that evaluated the effect of tight control of early Crohn disease and demonstrated the critical impact of deep remission in patients with recently diagnosed Crohn disease, researchers collected and analyzed long-term follow-up data of 122 patients with the disease.

The researchers observed that achieving deep remission early on was significantly associated with an 81% decrease in the risk of adverse outcomes over a median of 3 years. The data suggest strongly that achieving deep remission early in the course of Crohn disease can lead to disease modification with a significant decrease in long-term complications. This discovery may play a big role in slowing disease progression if it is possible to catch and treat Crohn disease early, according to the study authors.

Predicting Crohn Disease 5 Years Before First Symptoms

In a study of serum biomarkers of military personnel collected and stored by the US Department of Defense, researchers derived a predictive model of Crohn disease. In the PREDICTS study (Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects), researchers identified 51 protein biomarkers that were predictive of developing Crohn disease within 5 years before diagnosis with a 76% accuracy.

In total, the researchers evaluated 200 patients with Crohn disease, 199 with ulcerative colitis, and 200 controls. The study suggested that biological processes are activated many years before Crohn disease, opening the possibility of developing targeted strategies that could work to prevent or delay disease onset, according to the study authors.

“Although we recognize that a preventive strategy may still be many years down the road, studies analyzing samples taken years before diagnosis will likely contribute to a greater knowledge of disease pathogenesis and have the potential to help us improve treatments. When we combine this finding with the knowledge that early intervention can lead to better outcomes for our patients with Crohn disease, we have a truly relevant headline for a disease that has no cure,” said lead author Joana Torres, PhD, MD, in a press release.

First Study to Evaluate Association of Metal Exposure and IBD

In a study of metal exposure in the baby teeth of patients who eventually developed IBD later in life, researchers collected data from 28 adult Portuguese patients, taking advantage of the country’s long tradition of parents storing their children’s baby teeth. Investigators were able to retrieve the baby teeth of 12 patients with IBD and 16 unaffected controls, allowing them to study for the first time the association between early-life metal exposures and the future risk of IBD. Researchers investigated 4 metals, lead, copper, zinc, and chromium, and the developmental time periods during which exposure took place going back to the 25^th week of pregnancy.

Study of Ashkenazi Jewish Families Suggests Environmental Link

IBD has a long-established familial incidence and is approximately 4 times more prevalent in the Ashkenazi Jewish population, the researchers noted. In a study of IBD within Ashkenazi Jewish multiplex families, researchers studied 38 large families with 3 or more first-degree family members with IBD. The researchers hypothesized that, in a purely genetically inherited disease, affected siblings would be randomly distributed within the family. The researchers found that affected siblings were significantly more likely to be sequentially affected, with siblings with IBD clustering together within families.

"The clustering of affected siblings suggests there are factors beyond genetics that lead to the development of IBD in these multiplex families, likely attributable to a shared environment," said lead author Elizabeth Spencer, MD, in a press release. "We are continuing to follow these families in an effort to pinpoint the precise factors. If we can identify these factors, we could alter them as a preventative measure for those at high risk of developing IBD."

Reference

• Mount Sinai Researchers Unveil Mechanisms to Prevent Crohn’s Disease; Studies Describe Predictive Tools and Triggering Environmental Risk Factors Key to Prevention [news release]. Mount Sinai website. Published March 26, 2020. https://www.mountsinai.org/about/newsroom/2020/mount-sinai-researchers-unveil-mechanisms-to-prevent-crohns-disease-studies-describe-predictive-tools-and-triggering-environmental-risk-factors-key-to-prevention-pr. Accessed March 31, 2020.