Why METHYLOMIC?

The prime purpose of METHYLOMIC is to develop and clinically validate a novel epigenetic biomarker tool that enables the identification of most optimal treatments for individual patients and hence to ensure an effective and efficient use of existing and broadly prescribed biologicals for Crohn´s disease (CD). Thereby we will build on rapidly evolving DNA methylomics and machine learning technologies that tackle the hurdles currently encountered in the field. With close involvement of key-stakeholders and explorative studies in other chronic diseases (extrapolating our results to rheumatoid arthritis [RA] and the skin disease psoriasis [PsO]), we will push DNA methylation markers to become mainstream in clinical care in the next decades.

Below you will find information for:

Crohn’s Disease
Rheumatoid Arthritis
Psoriasis

For Crohn’s disease

Crohn’s Disease (CD) is a leading cause of chronic discomfort and disability affecting up to 1 in 300 people in Europe and North America, particularly affecting young productive individuals (15-40 years). In the EU alone, 78.000 CD cases are diagnosed every year. Extrapolating these numbers for the total European population indicates that there may be up to 1.6 million persons with CD.

Biological therapy has been shown to induce and maintain remission in Crohn’s disease (CD) patients but their efficacy to induce remission does not exceed 30-40%. At present, we are unable to predict whether an individual CD patient will respond to a certain biological therapy, which results in random treatment selection. Because serious complications (abscess, perforation, stenosis, metabolic deficiencies) often occur during periods of ineffective treatment, this ‘trial and error’ approach is associated with unnecessary health costs and a major negative impact on the patient’s quality of life. CD patients are often young and professionally active. Hence, the impact of suboptimal treatment selection is enormous.

Seeking a solution

The researchers will now work with several companies and patient organizations to develop a rapid test. Furthermore, they will evaluate if the test works in clinical practise by performing a clinical trial with 378 Crohn’s disease patients. Based on methylation markers in a patient’s blood, it will be determined which treatment will work best for that patient and that specific therapy will then be started. For comparison, a group of identical patients will be treated in the normal way without using the test. This will help determine whether the test leads to more effective treatments. Similar data will also be collected from patients with rheumatoid arthritis or psoriasis so that the test can be developed for these patient groups as well in the future.

For Rheumatoid Arthritis

Rheumatoid arthritis is a chronic, systemic disease which is characterized by inflammation of multiple joints that are usually affected symmetrically. Patients can also suffer from morning stiffness, malaise, fatigue and other symptoms. Approximately 1% of the European population if affected by the disease, making it a major impact on society. Before effective treatments were available, rheumatoid arthritis was characterized by progressive joint damage, resulting in irreversible joint deformities. Nowadays, more and more novel therapies are available to inhibit disease activity, called DMARDs (disease-modifying antirheumatic drugs). There drugs aim to prevent irreversible joint damage and lower disease activity as much as possible. However, it may be necessary to try different medicines, because patients do not benefit equally from each drug. It is important to start an effective therapy as soon as possible, as persistent inflammation can further damage the joints. Though, it is not yet possible to predict in advance which drug will have the desired effect.

Seeking a solution

The EPIPSORA trial will be carried out as part of the METHYLOMIC project. This study will investigate whether it is possible to develop and validate an epigenetic biomarker that predicts treatment success for rheumatoid arthritis and psoriasis. This would allow personalized management of the disease, and therefore lower further damage of the joints due to suboptimal treatment regimes. The study will investigate the treatment response of the commonly used drugs: adalimumab, tocilizumab and abatacept. Approximately 200 patients will be included.

For Psoriasis

Psoriasis (Pso) is a chronic, immune-mediated inflammatory disease (IMID) characterised by skin manifestations including but not limited to red, well-demarcated, endured and scaly plaques. The prevalence ranges between 0.09% and 11.43%, with higher numbers reported in Northern Europe. Approximately 64,6 million individuals are affected worldwide, with rising global incidence seen in the last 30 years. In approximately one-third of patients, more than 10% of the body is affected, and this is termed moderate-to-severe psoriasis. As there still is no cure for psoriasis until now, the need for treatment is typically lifelong and is mainly focused on disease remission.

Luckily, with the advent of newer and more effective therapies such as biologicals, the treatment goal has evolved towards (near) complete skin clearance, resulting in a new gold standard in clinical practice. Nevertheless, selecting the right biologic for an individual patient from the start remains challenging for the physician. Finding the best biologic for each patient is currently based on a process of ‘trial and error’, steered by clinical aspects, physicians’ expertise and patient characteristics e.g. baseline severity of disease, comorbidities, impairment of life quality, compliance profile, pregnancy wish, age and degree of professional activity.

Seeking a solution

The EPIPSORA trial will be carried out as part of the METHYLOMIC project. This study will investigate whether it is possible to develop and validate an epigenetic biomarker that predicts treatment success for rheumatoid arthritis and psoriasis. This would allow personalized management of the disease, and improve the patient’s quality of life. The study will investigate the treatment response of the commonly used drugs: adalimumab, ustekinumab and secukinumab. Approximately 200 patients will be included.