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Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial
  1. Iain B McInnes1,
  2. Joachim Sieper2,
  3. Jürgen Braun3,
  4. Paul Emery4,
  5. Désirée van der Heijde5,
  6. John D Isaacs6,
  7. Georg Dahmen7,
  8. Jürgen Wollenhaupt8,
  9. Hendrik Schulze-Koops9,
  10. Joseph Kogan10,
  11. Shenglin Ma11,
  12. Martin M Schumacher10,
  13. Arthur P Bertolino10,
  14. Wolfgang Hueber10,
  15. Paul P Tak12,13
  1. 1Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK
  2. 2Medical Department I, Rheumatology, Charité Campus Benjamin Franklin, Berlin, Germany
  3. 3Rheumazentrum Ruhrgebiet, Herne, Germany
  4. 4Section of Musculoskeletal Disease, University of Leeds and Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK
  5. 5Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  6. 6Musculoskeletal Research Group, Newcastle University and the Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK
  7. 7Praxis für Orthopädie, Extrakorporale Stoßwellen-Therapie, Hamburg, Germany
  8. 8Department of Rheumatology and Clinical Immunology, Schön Klinik Hamburg Eilbek, Hamburg, Germany
  9. 9Department of Rheumatology, Medizinische Klinik and Poliklinik IV, University of Munich, Munich, Germany
  10. 10Translational Medicine—Autoimmunity, Novartis Institutes for BioMedical Research, Basel, Switzerland
  11. 11Translational Medicine/BMD/MLA, China Novartis Institutes for BioMedical Research, Shanghai, China
  12. 12Department of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  13. 13Therapy Area Immunoinflammation, GlaxoSmithKline, Stevenage, UK
  1. Correspondence to Dr Wolfgang Hueber, Translational Medicine—Autoimmunity, Novartis Institutes for BioMedical Research, WSJ 386.10.48, Basel CH-4002, Switzerland; wolfgang.hueber{at}novartis.com

Abstract

Objective To evaluate the efficacy and safety of secukinumab, a fully human, anti-interleukin (IL)-17A monoclonal antibody, in patients with psoriatic arthritis (PsA).

Methods 42 patients with active PsA fulfilling ClASsification for Psoriatic ARthritis (CASPAR) criteria were randomly assigned (2:1) to receive two intravenous secukinumab doses (10 mg/kg; n=28) or placebo (n=14) 3 weeks apart. The primary endpoint was the proportion of American College of Rheumatology (ACR) 20 responses at week 6 for secukinumab versus placebo (one-sided p<0.1).

Results Primary endpoint: ACR20 responses at week 6 were 39% (9/23) for secukinumab versus 23% (3/13) for placebo (p=0.27). ACR20 responses were greater with secukinumab versus placebo at week 12 (39% (9/23) vs 15% (2/13), p=0.13) and week 24 (43% (10/23) vs 18% (2/11), p= 0.14). At week 6, ‘good’ European League Against Rheumatism response was seen in 21.7% (5/23) secukinumab versus 9.1% (1/11) placebo patients. Compared with placebo at week 6, significant reductions were observed among secukinumab recipients for C reactive protein (p=0.039), erythrocyte sedimentation rate (p=0.038), Health Assessment Questionnaire Disability Index (p=0.002) and Short Form Health Survey (SF-36; p=0.030) scores. The overall adverse event (AE) frequency was comparable between secukinumab (26 (93%)) and placebo (11 (79%)) recipients. Six serious AEs (SAEs) were reported in four secukinumab patients and one SAE in one placebo patient.

Conclusions Although the primary endpoint was not met, clinical responses, acute-phase reactant and quality of life improvements were greater with secukinumab versus placebo, suggesting some clinical benefit. Secukinumab exhibited satisfactory safety. Larger clinical trials of secukinumab in PsA are warranted.

  • Psoriatic Arthritis
  • Cytokines
  • TNF-alpha

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