Can genetic markers predict the response of TNF inhibitor therapy
The aim of the project is to identify genetic markers, which are associated with the treatment efficacy of TNF inhibitor treatment.
Rheumatoid arthritis (RA), psoriasis (PSA) and inflammatory bowel disease (IBD) are autoimmune diseases. The diseases share several similarities, and there are common genetic pathways involved in the etiology. Severe cases of RA, PSA and IBD are treated with TNF inhibitor. This treatment has significant side effects and one third of the patients have no effect of the treatment. There is an increasing understanding of the concept, that genetic may impact tratment effects. However, there are only sparsely data concerning genetic predictors of the treatment results for TNF inhibitor.
The aim of the project is...
to identify genetic markers, which are associated with the treatment efficacy of TNF inhibitor treatment
Our hypothesis is...
that genetic markers can predict the effect of TNF inhibitor treatment in patients with RA, PSA and IBD
This knowledge can be used to optimize the treatment of the individual patient (personalized treatment). Thereby, patients who are most likely to benefit from the treatment can be selected for anti-TNF treatment
that knowledge of the underlying biological mechanisms of the disease and treatment response can promote the development of new treatment strategies for RA, PSA and IBD
Description of the cohort
Blood samples analysed for tuberculosis antibodies from Danish laboratories have been collected since September 2009 and so far blood samples from approx. 30.000 patients have been collected in our biobank. Samples from patients with RA, PSA and IBD have been identified through the databases Danbio, Dermbio and The National Patient Registry. Cohorts of 538 patients with RA, 482 patients with Celiac Disease (CD) and 256 patients with Ulcerative colitis (UC) have been established. Replication cohorts of patients with RA and IBD and a new cohort of PSA are about to be established.
Data and biological material
The following data is retrieved from Danbio, Dermbio and/or the patient's medical records: Diagnosis, treatment response, age, gender, CD location and behaviour and UC distribution, course of the disease, age at diagnosis, smoking status at diagnosis, smoking status at treatment, operations, concomitant medication and familiar disposition.
Collaborating researchers and departments
Organmedical Clinic, Hospital of Southern Jutland, Aabenraa and Institute of Regional Health Research, University of Southern Denmark
- Associate Professor and Senior Hospital Physician Vibeke Andersen, PhD
Statens Serum Institut
- Head of Laboratory Paal Skytt Andersen, MSc, PhD
- Senior Scientist Vibeke Østergaard Thomsen
National Research Centre for the Working Environment, Copenhagen
Department of Rheumatology, Frederiksberg Hospital
Department of Internal Medicine, Regional Hospital Viborg
- PhD-student Steffen Bank, MSc
Hospital of Southern Jutland, Institute of Regional Health Research, University of Southern Denmark
- PhD-student Jacob Sode, MD
Dermbio, represented by Department of Dermatology, Roskilde Hospital
- Tomas Norman Dam, MD, PhD
Publications associated with the project
High-quality and -quantity DNA extraction from frozen archival blood clots for genotyping of single-nucleotide polymorphisms. / Bank S, Nexø BA, Andersen V, Vogel U, Andersen PS. Genet Test Mol Biomarkers. 2013 Jun;17(6):501-3. doi: 10.1089/gtmb.2012.0429. Epub 2013 Apr 10.
Anti-TNF Treatment Response in Rheumatoid Arthritis Patients Is Associated with Genetic Variation in the NLRP3-Inflammasome. / Sode J, Vogel U, Bank S, Andersen PS, Thomsen MK, Hetland ML et al. PloS one. 2014;9(6). e100361.
Associations between functional polymorphisms in the NF?B signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease. / Bank S, Andersen PS, Burisch J, Pedersen N, Roug S, Galsgaard J et al. Pharmacogenomics Journal. 2014;14:526–534.
Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort. / Bank, S., Andersen, P. S., Burisch, J., Pedersen, N., Roug, S., Galsgaard, J., Ydegaard Turino, S., Broder Brodersen, J., Rashid, S., Kaiser Rasmussen, B., Avlund, S., Bastholm Olesen, T., Hoffmann, H. J., Andersen Nexø, B., Sode, J., Vogel, U. & Andersen, V. 2015 I : PloS one. 10, 12
Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti-TNF Response in Patients with Rheumatoid Arthritis. / Sode, J., Vogel, U., Bank, S., Andersen, P. S., Hetland, M. L., Locht, H., Heegaard, N. H. H. & Andersen, V. 2015 I : PloS one. 10, 10, 13