Full project description ESR 10

ESR 10: Pharmacokinetics and immunogenicity of therapeutic antibodies in inflammatory bowel disease and spondyloarthritis: A RESEARCH PROJECT ON THE EDGE BETWEEN GASTROENTERLOGY AND RHEUMATOLOGY-POSITION FILLED

PhD research

Hosts:

Prof Dr Geert D’Haens

Gastroenterologist| Professor

Dr Marleen van de Sande

Rheumatologist| Assistant professor| PhD

Amsterdam University Medical Centers (location AMC)

Meibergdreef 9

105AZ  Amsterdam

The Netherlands

Duration: 48 months

Background

Therapeutic antibodies have become the cornerstone of effective treatment in inflammatory diseases of joints and gut. Several challenges, however, remain poorly investigated such as the prevention and treatment of immunogenicity, optimal dosing schedules and prediction of response/failure to individual mode of actions. The current project will investigate these questions in a collaborative project in inflammatory bowel disease and spondyloarthritis patients.

Approach 

Key objectives are : 1. Analyzing epigenetic profiles predicting response and failure to biological treatments. 2. Evaluate changes in immunogenicity to TNFi before and after adding methotrexate. 3. Analyze the difference in lymphoid tissue response to TNF inhibitors in patients with and without immunogenicity 4. Analyze difference in lymphoid tissue response in Crohn ‘s patients with and without fistula’s before and after treatment.

Our research team

It is our ambition to improve treatment outcome by personalized treatment choices based on molecular profiles as well as by optimizing dosing strategy and prevention of loss of efficacy due to immunogenicity. Within the AMC there is a close collaboration between the departments of rheumatology and gastroenterology. We are embedded in the Amsterdam Infection and Immunity research Institute as well as in the Amsterdam Gastroenterology and Metabolism research institute and Tytgat institute. We have access to high quality core research facilities of the AMC. This provides an excellent multidisciplinary research environment which form a basis for fruitful scientific collaborations between clinicians and basic scientists on our translational research projects. Prof Geert D’Haens is gastroenterologist and global key opinion leader in inflammatory bowel disease with a strong translational and pharmacokinetic profile. Dr. Marleen van de Sande is rheumatologist and has a translational research line on immunopathogenesis of very early spondyloarthritis. This project will be performed in close collaboration with ARCAID PI’s dr. Lisa van Baarsen (transciptomics, lymph node tissue responses), and with the radiology department.