Mechanism of Action of Anti-IL17 Therapy in Peripheral Spondyloarthritis
Condition: Spondylarthropathies
MeSH terms: Spondylitis; Spondylarthritis; Spondylarthropathies
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to determine the mechanism of action on target tissue level of
      anti Interleukine-17 (anti-IL-17) an therapy in peripheral spondyloarthritis.

      Patients will be treated with anti-IL-17 therapy (secukinumab) for 12 weeks and with a 2 year
      extension period thereafter.

      At week 0 and 12 peripheral blood, synovial tissue and skin will be analysed with different
      techniques, including immunohistochemistry, RNA analysis and tissue culture to assess the
      effect of the therapy on inflammatory pathways.
    

Detailed description: 
      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).
    

Intervention name(s): Secukinumab
Intervention type(s): Drug
Intervention description(s): anti IL17 therapy (subcutaneous)
Other intervention name(s): AIN457
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Peripheral Spondylarthropathies; Psoriatic arthritis; Reactive arthritis