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OP0168 Secukinumab Significantly Improves Signs and Symptoms of Active Ankylosing Spondylitis: 52-Week Data from Measure 2, A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial with Subcutaneous Loading and Maintenance Dosing
  1. J. Sieper1,
  2. J. Braun2,
  3. X. Baraliakos2,
  4. D.L. Baeten3,
  5. M. Dougados4,
  6. P. Emery5,
  7. A. Deodhar6,
  8. J. C.-C. Wei7,
  9. B. Porter8,
  10. M. Andersson9,
  11. S. Mpofu9,
  12. H. Richards9
  1. 1Charité University Medicine Berlin, Berlin
  2. 2Rheumazentrum Ruhrgebiet, Herne, Germany
  3. 3Academic Medical Center, Amsterdam, Netherlands
  4. 4Université Paris René Descartes and Hôpital Cochin, Paris, France
  5. 5University of Leeds, Leeds, United Kingdom
  6. 6Oregon Health & Science University, Portland, United States
  7. 7Chung Shan Medical University Hospital, Taichung, Taiwan, Province of China
  8. 8Novartis Pharmaceuticals Corporation, East Hanover, United States
  9. 9Novartis Pharma AG, Basel, Switzerland

Abstract

Background In MEASURE 2 (NCT01649375), subcutaneous (s.c.) administration of secukinumab improved the signs and symptoms of ankylosing spondylitis (AS) through 16 weeks (wks) of therapy.1

Objectives To investigate the long-term (52 wks) efficacy and safety of s.c. secukinumab in the MEASURE 2 study.

Methods 219 adults with active AS, despite therapy with nonsteroidal anti-inflammatory drugs, were randomized to receive s.c. secukinumab 150 mg, 75 mg, or placebo (PBO) at baseline, Wk 1, 2, and 3, and every 4 wks starting from Wk 4. At Wk 16, subjects in the PBO group were re-randomized to secukinumab 150 mg or 75 mg every 4 wks. The primary endpoint was the proportion of subjects achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 response at Wk 16. Secondary endpoints included ASAS40, high sensitivity C-reactive protein (hsCRP), ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity (BASDAI), Short Form-36 Health Survey Physical Component Summary (SF-36 PCS), Ankylosing Spondylitis Quality of Life (ASQoL), and ASAS partial remission. Statistical analyses at Wk 16 used non-responder imputation (binary variables) and mixed-effects repeated measures model (continuous variables) following a pre-defined hierarchical hypothesis testing strategy to adjust for multiplicity of testing. Wk 52 data are as observed.

Results 181 pts (82.6%) completed 52 wks of treatment. ASAS20 response rate at Wk 16 was 61.1% with secukinumab 150 mg vs 28.4% with PBO (P=0.0001). Secukinumab 150 mg also significantly improved hsCRP, ASAS40, ASAS 5/6, BASDAI, SF-36 PCS and ASQoL at Wk 16, compared with PBO. Clinical responses with secukinumab 75 mg did not reach statistical significance for any of the pre-specified endpoints based on hierarchical testing. Improvements with secukinumab 150 mg were sustained through Wk 52; ASAS20/40 response rates with secukinumab 150 mg were 73.8%/57.4% at Wk 52 (observed data). ASAS20/40 response rates in subjects originally randomized to PBO who received secukinumab 150 mg (n=34) were 75.0%/56.3% at Wk 52. Exposure-adjusted adverse event (AE) rates (mean secukinumab exposure: 425.8 days; mean PBO exposure: 107.6 days) were 214.1, 211.7 and 443.2 per 100 patient-years with secukinumab 150 mg, 75 mg and PBO, respectively. The respective rates of serious AEs were 6.6, 7.7 and 14.0. The most common serious AE (SAE) was serious infections; no subject discontinued therapy due to a SAE.

Conclusions Secukinumab 150 mg s.c. provided sustained improvements to 52 weeks in the signs and symptoms of AS, reducing inflammation, and improving physical function and health-related quality of life. Secukinumab was well tolerated; safety findings were consistent with previous reports.

References

  1. Sieper J, et al. Arthritis Rheumatol. 2014;66(11Suppl):S232

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

Disclosure of Interest J. Sieper Grant/research support from: AbbVie, Pfizer, and Merck, Consultant for: AbbVie, Pfizer, Merck, UCB, and Novartis, Speakers bureau: AbbVie, Pfizer, Merck, and UCB, J. Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB, Consultant for: Abbvie (Abbott), Amgen, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB, X. Baraliakos Grant/research support from: AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, Consultant for: AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, Speakers bureau: AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, D. Baeten Grant/research support from: Boehringer-Ingelheim, Janssen, MSD, Novartis, and Pfizer, Consultant for: AbbVie, Boehringer-Ingelheim, BMS, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, M. Dougados Grant/research support from: AbbVie, BMS, Eli Lilly, Merck, and Pfizer, Consultant for: Eli Lilly, P. Emery Consultant for: AbbVie, BMS, Merck, Novartis, Pfizer, Roche, and UCB, A. Deodhar Grant/research support from: AbbVie, Celgene, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Celgene, Janssen, Novartis, Pfizer, and UCB, J. Wei Grant/research support from: BMS, Janssen, Pfizer, Sanofi-Aventis, and Novartis, Consultant for: Pfizer, Celgene, Chugai, UCB Pharma, and TSH Taiwan, Speakers bureau: Abbott, BMS, Chugai, Eisai, Janssen, and Pfizer, B. Porter Shareholder of: Novartis, Employee of: Novartis, M. Andersson Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, H. Richards Employee of: Novartis

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