Spondyloarthritis (SpA) is a common chronic inflammatory rheumatic disease, with a prevalence of about 0.5%. In addition to the disabling rheumatic manifestations, some SpA patients develop severe extra-articular manifestations such as inflammatory bowel disease, uveitis and psoriasis. SpA mainly affects young adults and the functional consequences of inadequately controlled disease alter both their quality of life and their professional capacity with direct impact on healthcare costs.
The proinflammatory cytokines TNF and IL-17A are pivotal pathogenic cytokines in SpA and the introduction of biological therapies targeting these two cytokines has revolutionized the treatment of this disease. However, 30 to 40% of patients do not respond to these agents, and are exposed to the potential side-effects of the drugs without clinical benefit. The reasons underlying unresponsiveness are not known and it is currently not possible to predict therapeutic responses to these therapies. Defining the mechanisms of action of TNF-blockers and IL-17A inhibitors and developing personalized treatment strategies for patients affected by SpA and other chronic inflammatory diseases are therefore urgent medical and societal needs.
The premise of this project is that therapeutic outcome is defined by the unique interaction of the drug with the biological characteristics of each patient. Improved understanding of the molecular mechanisms of drug action in individual patients is key for the successful implementation of personalized treatment strategies and may identify novel therapeutic targets. In this project, we perform a comprehensive characterization of the cellular, functional and molecular effects of TNF-blockers and IL-17A-inhibitors on immune responses in SpA patients.