Blood Test May Predict Crohn's Disease 2 Years Before Onset

Medscape

21-05-2025

SAN DIEGO — Crohn's disease (CD) has become more common in the United States, and an estimated 1 million Americans have the condition. Still, much is unknown about how to evaluate the individual risk for the disease.
'It's pretty much accepted that Crohn's disease does not begin at diagnosis,' said Ryan Ungaro, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, speaking at Digestive Disease Week (DDW) 2025.
Although individual blood markers have been associated with the future risk for CD, what's needed, he said, is to understand which combination of biomarkers are most predictive.
Now, Ungaro and his team have developed a risk score they found accurate in predicting CD onset within 2 years before its onset.
It's an early version that will likely be further improved and needs additional validation, Ungaro told Medscape Medical News .
'Once we can accurately identify individuals at risk for developing Crohn's disease, we can then imagine a number of potential interventions,' Ungaro said.
Approaches would vary depending on how far away the onset is estimated to be. For people who likely wouldn't develop disease for many years, one intervention might be close monitoring to enable diagnosis in the earliest stages, when treatment works best, he said. Someone at a high risk of developing CD in the next 2 or 3 years, on the other hand, might be offered a pharmaceutical intervention.
Developing and Testing the Risk Score
To develop the risk score, Ungaro and colleagues analyzed data of 200 patients with CD and 100 healthy control participants from PREDICTS, a nested case-controlled study of active US military service members. The study is within the larger Department of Defense Serum Repository, which began in 1985 and has more than 62.5 million samples, all stored at −30 °C.
The researchers collected serum samples at four timepoints up to 6 or more years before the diagnosis. They assayed antimicrobial antibodies using the Prometheus Laboratories platform, proteomic markers using the Olink inflammation panel, and anti–granulocyte macrophage colony-stimulating factor autoantibodies using enzyme-linked immunosorbent assay.
Participants (median age, 33 years for both groups) were randomly divided into equally sized training and testing sets. In both the group, 83% of patients were White and about 90% were men.
Time-varying trajectories of marker abundance were estimated for each biomarker. Then, logistic regression modeled disease status as a function of each marker for different timepoints and multivariate modeling was performed via logistic LASSO regression.
A risk score to predict CD onset within 2 years was developed. Prediction models were fit on the testing set and predictive performance evaluated using receiver operating characteristic curves and area under the curve (AUC).
Blood proteins and antibodies have differing associations with CD depending on the time before diagnosis, the researchers found.
The integrative model to predict CD onset within 2 years incorporated 10 biomarkers associated significantly with CD onset.
The AUC for the model was 0.87 (considered good, with 1 indicating perfect discrimination). It produced a specificity of 99% and a positive predictive value of 84%.
The researchers stratified the model scores into quartiles and found the CD incidence within 2 years increased from 2% in the first quartile to 57.7% in the fourth. The relative risk of developing CD in the top quartile individuals vs lower quartile individuals was 10.4.
The serologic and proteomic markers show dynamic changes years before the diagnosis, Ungaro said.
A Strong Start
The research represents 'an ambitious and exciting frontier for the future of IBD [inflammatory bowel disease] care,' said Victor G. Chedid, MD, MS, consultant and assistant professor of medicine at Mayo Clinic, Rochester, Minnesota, who reviewed the findings but was not involved in the study.
Currently, physicians treat IBD once it manifests, and it's difficult to predict who will get CD, he said.
The integrative model's AUC of 0.87 is impressive, and its specificity and positive predictive value levels show it is highly accurate in predicting the onset of CD within 2 years, Chedid added.
Further validation in larger and more diverse population is needed, Chedid said, but he sees the potential for the model to be practical in clinical practice.
'Additionally, the use of blood-based biomarkers makes the model relatively noninvasive and easy to implement in a clinical setting,' he said.
Now, the research goal is to understand the best biomarkers for characterizing the different preclinical phases of CD and to test different interventions in prevention trials, Ungaro told Medscape Medical News .
A few trials are planned or ongoing, he noted. The trial PIONIR trial will look at the impact of a specific diet on the risk of developing CD, and the INTERCEPT trial aims to develop a blood-based risk score that can identify individuals with a high risk of developing CD within 5 years after initial evaluation.
Ungaro reported being on the advisory board of and/or receiving speaker or consulting fees from AbbVie, Bristol Myer Squibb, Celltrion, ECM Therapeutics, Genentech, Jansen, Eli Lilly, Pfizer, Roivant, Sanofi, and Takeda. Chedid reported having no relevant disclosures.