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O015 Il-17 blockade with secukinumab in peripheral spondyloarthritis impacts synovial immunopathology without compromising systemic immune responses
  1. M van de Sande1,
  2. L van Mens1,
  3. S Menegatti2,
  4. I Blijdorp1,
  5. J de Jong1,
  6. I Fluri1,
  7. T Latuhihin1,
  8. A van Kuijk3,
  9. L Rogge2,
  10. N Yeremenko1,
  11. D Baeten1
  1. 1Clinical Immunology and Rheumatology, Amsterdam Rheumatology and immunology Centre, Academic Medical Center-University of Amsterdam, Amsterdam, Netherlands
  2. 2Immunoregulation Unit, Institut Pasteur, Paris, France
  3. 3Amsterdam Rheumatology and immunology Centre, Reade, Amsterdam, Netherlands

Abstract

Introduction Secukinumab (anti-IL-17A) is an effective therapy for ankylosing spondylitis(AS) and psoriatic arthritis (PsA), the prototypical forms of spondyloarthritis (SpA).

Objectives This study assessed if secukinumab modulates the immunopathology of target lesions without blunting systemic immune responses, using peripheral SpA (pSpA) as model.

Methods 20 active peripheral SpA patients were included in a 12 week open-label trial with secukinumab (300 mg weekly for 4 weeks followed by every 4 weeks). Outcomes included clinical response, cytokine production by peripheral blood cells using TruCulture technology, and histological and qPCR analysis of synovial biopsies before and after treatment.

Results All patients completed the 12 week study, without SAEs or severe treatment-related AEs. The primary efficacy endpoint, EULAR DAS 28 response at wk 12, was achieved by 18/20 patients (10 good and 8 moderate responders), with rapid and significant improvements in all clinical disease activity measurements. Clinical improvement in joint counts was associated with histological decrease in synovial sublining macrophages (p=0.028) and neutrophils (p=0.004), sensitive synovial biomarkers of response in pSpA, as well as with decreased synovial expression of IL-17A (p=0.010) but not TNF. Systemically, secukinumab treatment decreased CRP (p<0.01) and ESR (p<0.01), as well as MMP-3 production in the truculture system (p<0.01). With exception of IL-17A itself, however, the capacity of peripheral blood cells to produce a broad panel of cytokines and chemokines upon stimulation with microbial antigens was not affected.

Conclusions This mechanism-of-action study in pSpA indicates that clinical improvement upon secukinumab treatment is paralleled by immunomodulation of the inflamed target tissues without compromising systemic immune responses.

Disclosure of interest M. van de Sande Grant/research support from: Novartis, Eli Lilly, Boehringer Ingelheim, Consultant for: Abbvie, Novartis, Speakers bureau: x, L. van Mens: None declared, S. Menegatti: None declared, I. Blijdorp: None declared, J. de Jong: None declared, I. Fluri: None declared, T. Latuhihin: None declared, A. van Kuijk Grant/research support from: x, Consultant for: Novartis, Celgene, L. Rogge: None declared, N. Yeremenko: None declared, D. Baeten Grant/research support from: Pfizer, MSD, Abbvie, UCB, Novartis, Janssen, Boehringer Ingelheim, Consultant for: Pfizer, MSD, Abbvie, UCB, Novartis, Janssen, Boehringer Ingelheim, Eli Lily, Roche, BMS, Glenmark, Employee of: UCB

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