Crohn's disease is a chronic inflammatory disease of the intestinal tract, which mainly affects adolescents and young adults. They then develop symptoms such as abdominal pain and diarrhoea, intestinal obstructions and weight loss. To investigate how this disease can be prevented, the INTERCEPT consortium wants to conduct three major studies over the next five years.
Verifying biomarkers
First of all, the researchers will analyse to how accurate the current predictions really are. Predictions are made by identifying which patients have certain biomarkers. In Crohn's disease, a number of biomarkers have previously been identified by examining blood from a US Army biobank and the researchers aim to see if these are really the perfect indicators.
"American soldiers give blood every year. Soldiers who contracted Crohn's disease had previously been examined for blood taken from the biobank. This showed that long before someone got the disease – sometimes up to 7 years – certain molecules could already be seen in the blood. Now we want to investigate among large groups of patients whether these molecules are indeed the right biomarkers for Crohn's disease. To do this, we are going to examine blood from European biobanks on a large scale," explains D'Haens. These include the Lifelines cohort in Groningen and the STATENS Serum Institute biobank in Denmark.
The research should not only provide clarity about which biomarkers predict the disease but also shed light on the individual importance of each of these biomarkers is. "Not every biomarker weighs equally in the prediction. We run a calculation on each biomarker; The result of that calculation is called the serum signature and indicates how high an individual's risk of getting Crohn's disease is," adds D'Haens
Testing, testing, testing
Crohn's regularly runs in families and the second stap gives attention to the hereditary nature of the disease. The researchers will first test the serum signature on 10,000 first-degree relatives of European patients across seven countries: the Netherlands, France, Spain, Portugal, Poland, Italy and Sweden. Those who test positively for the serum signature will then receive a stool examination and, if necessary, a bowel examination.
Stop Crohn's
In the final step of the project, the researchers will follow 80 people with a high risk of Crohn's disease for two years. D'Haens says: "We plan to examine the stool for inflammatory cells, an increase indicates that the participant probably has the early stage of Crohn's. We will then zoom in on these participants, through questionnaires but also through the use of an endoscopy," adds D'Haens. Subsequently, a portion will receive early treatment with the drug vedolizumab and the remaining patients, a placebo. Vedolizumab is already used as a treatment for Crohn's, but the researchers hope that it will also stop the development of the disease at an early stage.
Point on the horizon
D'Haens personally believes that studies like this can make an important contribution to the prevention of Crohn's and a number of other immune disorders such as type 1 diabetes, rheumatism and multiple sclerosis. "If adults are screened for risks with a blood test every 5 years in the future, doctors can use therapy in a timely and selective manner to prevent disease. The patient remains healthy and does not compromise on quality of life. Hospitalizations, operations, loss of work are not an issue. The impact on society is enormous," he concludes.
To participate in this study, intensive cooperation is sought with the patient associations. In due course, they can reach potential participants via their social media channels and ask if they are willing to register with Amsterdam UMC, UMC Utrecht or UMC Groningen.
INTERCEPT is a collaboration of a large group of academic partners in the Netherlands, France, Spain, Italy, Portugal, Poland, Sweden, Norway, Denmark, England and North America. There is further support from the biomedical industry (Takeda, Ludger, Prometheus Laboratories and Celltrion), from the United European Gastroenterology Federation (UEGF) and the European Patient Association EFCCA. The grant amounts to 37.5 million euros for 5 years and is coordinated by Geert D'Haens (MDL physician specializing in Crohn's and head of department Amsterdam UMC), Wouter de Jonge (Tytgat Lab, Amsterdam UMC), Jean-Frédéric Colombel and Ryan Ungaro (Mount Sinai New York), Joana Torres (Lisbon), Jonas Halvarsson (Orebrö) and Rinse Weersma (Groningen).