Predicting the severity of inflammatory bowel disease (IBD) has long been a challenge for clinicians, but a large Danish study reveals a genetic risk score can now forecast disease course at the time of diagnosis.
Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, “are characterized by inflammation of the wall of a part of the digestive tract, due to a deregulation of the intestinal immune system,” according to the Inserm. These conditions can be particularly disabling and disrupt the daily lives of those affected. IBD represents a significant public health issue, affecting approximately 200,000 to 300,000 people in France, with the incidence steadily increasing year after year. Given this alarming global trend, the medical community is continually seeking innovative solutions to anticipate complications and tailor treatment protocols.
IBD: Treatments are Tough to Adapt
One of the major challenges for doctors treating IBD is the difficulty – if not impossibility – of predicting whether a patient will develop a mild form of the disease or a debilitating course, sometimes leading to major surgery or the need for a stoma. This lack of predictive tools creates obvious risks. Some patients receive unnecessary overtreatment, even as others suffer from undertreatment.
This situation delays decisive interventions before irreversible damage to the intestine occurs. To address this gap, researchers at Aalborg University in Denmark analyzed the medical records of more than 8,300 patients from national health registries. The results of their function, published in February of this year, offer promising new perspectives for patients. The findings could facilitate personalize treatment plans and improve outcomes for individuals living with IBD.
A Genetic Score to Assess Severity
According to the study published in the scientific journal Gastroenterology, predicting disease progression is now possible. The team used polygenic scores to measure the cumulative effect of genetic variants linked to disease development. The results clearly demonstrate that patients with the highest genetic score have a 2.74 times higher risk of major surgery for Crohn’s disease and a 2.04 times higher risk for ulcerative colitis (also known as rectocolitis hemorragique). Biologically, this high risk is reflected in significantly elevated blood levels of fecal calprotectin, a strong indicator of intestinal inflammation, and C-reactive protein. Analyses also reveal a significant decrease in hemoglobin levels. These profiles more frequently require aggressive treatments such as biologics, immunomodulators, or intensive courses of corticosteroids.
Distinct Mechanisms Depending on the Condition
Another key finding of the study is that behaviors differ significantly depending on the specific condition. In the case of Crohn’s disease, the link between DNA and severity primarily depends on the extent of inflammation along the intestinal tract. Conversely, for ulcerative colitis, severity is correlated with the genetic load regardless of the extent of the lesions. The authors emphasize that a common architecture links susceptibility to the disease and its virulence. The results confirm the crucial role of the HLA-DRB1*01:03 gene as a marker of worsening disease, significantly increasing the likelihood of surgery.
Toward Personalized Patient Monitoring
The future goal is to utilize this DNA analysis at the time of initial diagnosis to immediately identify individuals who require increased monitoring and targeted therapy. Anticipating disease progression could significantly reduce structural damage to the digestive organs. However, genetics is not the whole picture. Experts believe it must be combined with a rigorous analysis of lifestyle and the state of the gut microbiome to provide a perfect prognosis. “We hope that the results will allow doctors to propose more precise treatments in the future, so that a greater number of patients can benefit from a much less severe course of the disease,” concluded Marie Vibeke Vestergaard, the study’s lead author.
