Crohn's Disease

Background

Researchers from Amsterdam UMC and Oxford have discovered that certain molecules (methyl groups) on Crohn´s disease (CD) patients’ DNA (so-called methylation marks*) can predict with a high level of confidence whether a patient will respond to a particular biologic treatment. This is of great importance because the vast majority (more than 60%) of patients with Crohn’s disease do not respond properly to these modern treatments. At present, it is impossible to predict in advance which treatment will be most effective. This leads to long periods of insufficient disease control which can result in disease flares and, more importantly, complications which often need to be treated surgically. All this increases the disease burden for the patients as well as the social costs (loss of productivity). For long, there has been an unmet need for more personalized treatment decisions for each individual patient.

*What are DNA methylation marks?

Epigenetics are changes to your DNA which do not alter the sequence of your DNA, but only change how certain proteins read your DNA sequence. This enables to turn certain genes “on” or “off”. DNA methylation is an epigenetic mechanisms where a chemical group (a methyl group) is added to the DNA. Usually, this methyl group is placed at specific places on the DNA where it can block proteins to attach to the DNA and “read” the gene. In general this means that DNA methylation turns genes “off”.

OMICROHN Trial

The IBD research group at Amsterdam UMC in collaboration with a consortium of 17 partners and patient organizations are currently developing a rapid blood test that will predict response to the biologic treatments adalimumab, vedolizumab and ustekinumab, the most frequently used medications for CD. The blood test will be “clinically validated” in a clinical trial with 400 patients with CD in various countries. Based on the individual patient’s blood test, treatment with the highest likelihood of success will be initiated. For comparison, a ‘control’ group of comparable CD patients will be treated in the usual way, without using the test. This clinical trial will determine whether the test leads to more effective treatments.

The OMICROHN Trial will start in September 2024 in a large number of European hospitals, and will take 3 years to complete. The research is funded by the European Union (Horizon Europe) grant of more than 10 million euros.

Helmsley Charitable Trust has granted additional funding to support the following clinical validation trial activities:

  1. Project site and data management that is aligned with the strict regulatory agency standards to allow the future submission of the trial data and analysis for regulatory approval of the assay.
  2. Central reading of endoscopies to enhance the overall quality of the trial.
  3. Training, quality control, and central reading for intestinal ultrasound (IUS) in one-third of trial participants. IUS transmural healing will be an exploratory outcome for the proposed trial.
  4. Processing of biopsy samples and central histology reading for analysis of disease activity.
  5. Recruitment boosting activities across the countries of the participating clinical sites including remittance of investigator participation fees, site staff training, periodic trial newsletters, and a national kick-off and two national site meetings of the investigators.
  6. Trial oversight, scientific support, and medical writing for clinical trial reports and publications.
Patient informationPatient Information – GeneralCrohn’s Disease