Mechanism of Action of Anti-IL17 Therapy in Peripheral Spondyloarthritis

Background of the study: Spondyloarthritis is the second most frequent form of chronic inflammatory arthritis with a prevalence of 0.5%. It effects mainly young adults and leads to major functional handicap due to inflammation of axial and peripheral joints as well as progressive ankylosis and structural damage. In the late nineties Tumor Necrosis Factor (TNF) blockade was introduced as a successful treatment, but: only 50% responds well and tolerates, a-TNF does not halt the structural damage and TNF blockade does not induce long lasting remission as almost all patients relapse within a few weeks after interruption of the treatment. There is thus a high unmet need for alternatives. The rationale for anti-IL17 therapy is based on various auto-inflammatory and auto immune models, preliminary efficacy data in psoriasis and Rheumatoid arthritis (RA) and an association of SpA with Interleukin 23 Receptor (IL23R) single nucleotide polymorphism (SNP). Efficacy data on anti-IL17 shows that it is a highly effective treatment for signs and symptoms in SpA, moreover sub-analysis of the anti-TNF naïve patients shows the same trend. Objective of the study: To assess molecular and cellular effects of the treatment on the synovium. Secondary: To compare which molecular and cellular disease pathways are affected by IL-17 blockade and not by TNF blockade and thereby identify molecular biomarkers which may help to determine which patients may benefit form this treatment in comparison with anti-TNF treatment. To assess wether AIN457 silences vessel wall inflammation (by means of 18F-FDG PET(positron emission tomography)/CT of the carotic arteries and aorta. Study design: Single centre, 12-week open label study in subjects with clinically active peripheral spondylarthritis, with open label extension up to 2 years. Synovial biopsies and 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (18F FDG) PET/CT of the aorta and carotid arteries will be obtained from patients before and after 12 weeks of treatment with secukinumab. Study population: Patients with a diagnosis of spondyloarthritis according to the European Spondyloarthropathy Study Group (ESSG) or Assess Spondyloarthritis to international Society (ASAS) criteria with at least one swollen knee or ankle joint. Intervention : Secukinumab (AIN457) by subcutaneous injections (weekly for the first 4 weeks and every 4 weeks thereafter).