Work Package 4

Strategy

The overall aim of this WP is to confirm the potential of DNA methylation markers for the prediction of biological therapy success in RA and PsO. Similar to CD, biological therapies are also partly effective for RA. However, remission upon biological therapy is achieved in less than 50% of RA cases. For PsO, biological therapy success is better, but a stratification is certainly needed as well. There are limited tools to help clinicians select the most appropriate biological for these patients. A pilot study conducted at AMC and Reade Amsterdam, identified epigenetic marks in RA patients (50 responders vs. 43 non-responders) that predict biological therapy response in patients treated with anti-TNF. Our prior work on CD patients make it logical to establish discovery and validation cohorts to identify patterns of epigenetic biomarkers in the blood of patients with RA, similar as to CD. Three centres of expertise in RA and renowned clinical trial units are committed to collaborate in this work.

Output

Sampling (n=400) from discovery and validation RA and PsO cohorts completed, predictive algorithms validated, and methylation assays designed.

Innovative elements

•  Pivotal collaboration among gastroenterologists, dermatologists, and rheumatologists on diseases with common underlying mechanisms
• Use of stringent and validated endpoints in an observational trial
• Remote and cross-site monitoring and data management.

Partners

Three clinical RA and PsO centers of expertise (Instituto de Medicina Molecular João Lobo Antunes, Ghent University, and Amsterdam University Medical Centres – location AMC) with ongoing cohort studies of patients on 3 commonly prescribed biologicals.