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THU0425 Secukinumab Improves Signs and Symptoms of Active Psoriatic Arthritis in a Phase 3 Randomized, Multicenter, Double-Blind, Placebo-Controlled Study Using a Subcutaneous Dosing Regimen (Future 2)
  1. I.B. McInnes1,
  2. P. Mease2,
  3. B. Kirkham3,
  4. A. Kavanaugh4,
  5. C. Ritchlin5,
  6. P. Rahman6,
  7. D. van der Heijde7,
  8. R. Landewé8,
  9. P.G. Conaghan9,
  10. A.B. Gottlieb10,
  11. H. Richards11,
  12. G. Ligozio12,
  13. L. Pricop12,
  14. S. Mpofu11
  1. 1University of Glasgow, Glasgow, United Kingdom
  2. 2Swedish Medical Center and University of Washington, Seattle, United States
  3. 3Guy's and St Thomas' Hospital, London, United Kingdom
  4. 4University of California, San Diego School of Medicine, La Jolla
  5. 5University of Rochester Medical Center, New York, United States
  6. 6Memorial University, St John's, Canada
  7. 7Leiden University Medical Center, Leiden
  8. 8University of Amsterdam and Atrium Medical Center, Amsterdam, Netherlands
  9. 9University of Leeds, Leeds, United Kingdom
  10. 10Tufts Medical Center, Boston, United States
  11. 11Novartis Pharma AG, Basel, Switzerland
  12. 12Novartis Pharmaceuticals Corporation, East Hanover, United States

Abstract

Background Secukinumab, a human anti–IL-17A monoclonal antibody, has demonstrated efficacy with an intravenous loading and subcutaneous (s.c.) maintenance regimen in psoriatic arthritis (PsA) (FUTURE 1; NCT01392326).

Objectives To evaluate the efficacy and safety of s.c. loading and maintenance dosing with secukinumab in FUTURE 2 (NCT01752634), a randomized, double-blind, placebo (PBO)-controlled phase 3 study in patients (pts) with active PsA.

Methods 397 adults with active PsA were randomized to s.c. secukinumab (300, 150 or 75 mg) or PBO at baseline, Week (Wk) 1, 2, 3, 4 and then every 4 wks thereafter. Randomization was stratified by prior exposure to anti-TNF therapy. The primary endpoint was ACR20 response at Wk 24. Secondary endpoints included PASI 75/90, Disease Activity Score 28 using C-reactive protein (DAS28-CRP), Short Form-36 Physical Component Summary (SF-36 PCS), Health Assessment Questionnaire-Disability Index (HAQ-DI), ACR50, dactylitis and enthesitis. Primary and secondary endpoints were included in a hierarchical testing analysis to adjust for multiplicity.

Results At Wk 24, ACR20 responses were significantly greater with secukinumab 300, 150 and 75 mg than PBO: 54.0%, 51.0% and 29.3% vs 15.3%, respectively (P<0.0001 for secukinumab 300 and 150 mg; P <0.05 for 75 mg vs PBO). Secukinumab 300 and 150 mg also improved secondary endpoints, including significant improvements in PASI 75/90 scores and DAS-28 CRP vs PBO (Table). Exposure-adjusted rates of treatment-emergent AEs (maximum exposure to secukinumab: 372 days) were 222.2 and 309.3 per 100 pt-years amongst secukinumab (pooled) and PBO-treated subjects, respectively. The respective rates of serious AEs were 7.8 and 8.8.

Conclusions Secukinumab 300 and 150 mg s.c. demonstrated clinically significant improvements in the signs and symptoms of PsA. The safety profile of secukinumab was satisfactory, suggesting that the drug is thus far well tolerated.

Acknowledgements Medical writing support was provided by Rachel Mason at Seren Communications (Tytherington, UK), and was funded by Novartis.

Disclosure of Interest I. McInnes Consultant for: Novartis, Amgen, Janssen, BMS, Pfizer, UCB, Abbvie, Celgene, and Lilly, P. Mease Grant/research support from: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, Consultant for: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Covagen, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, Speakers bureau: AbbVie, Amgen, Biogen Idec, BMS, Crescendo, Janssen, Lilly, Pfizer, and UCB, B. Kirkham Grant/research support from: AbbVie and UCB, Consultant for: Novartis, AbbVie, BMS, Lilly, and MSD, Speakers bureau: BMS, MSD, and UCB, A. Kavanaugh Consultant for: Novartis, C. Ritchlin Grant/research support from: Amgen and UCB, Consultant for: Novartis, P. Rahman Consultant for: Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, Pfizer, and Roche. Consultant to pharmaceutical companies dealing with biologic agents in rheumatology, D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, and Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, and Vertex, Paid instructor for: Director of Imaging Rheumatology bv, R. Landewé Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, Consultant for: Abbott/AbbVie, Ablynx, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, GlaxoSmithKline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, Paid instructor for: Director of Rheumatology Consultancy BV, which is a registered company under Dutch law, Speakers bureau: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, P. Conaghan Consultant for: Abbvie, Merck, Roche, Pfizer, Novartis, and UCB, Speakers bureau: Abbvie, Merck, Roche, Pfizer, Novartis, and UCB, A. Gottlieb Grant/research support from: Centocor (Janssen), Amgen, Abbott (Abbvie), Novartis, Celgene, Pfizer, Lilly, Coronado, Levia, Merck, and Xenoport, Consultant for: Amgen Inc., Astellas, Akros, Centocor (Janssen), Inc. Celgene Corp., Bristol-Myers Squibb Co., Beiersdorf, Inc., Abbott Labs. (Abbvie), DUSA, TEVA, Actelion, UCB, Novo Nordisk, Novartis, Dermipsor Ltd., Incyte, Pfizer, Canfite, Lilly, Coronado, Vertex, Karyopharm, CSL Behring Biotherapies for Life, GlaxoSmithKline, Xenoport, Catabasis, and Sanofi-Aventis, H. Richards Employee of: Novartis, G. Ligozio Shareholder of: Novartis, Employee of: Novartis, L. Pricop Shareholder of: Novartis, Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis

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