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
Authors: J. Sieper, J. Braun, X. Baraliakos, D.L. Baeten, M. Dougados, P. Emery, A. Deodhar, J. C.-C. Wei, B. Porter, M. Andersson, S. Mpofu, H. Richards
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> 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.<sup>1</sup> <h3>Objectives</h3> To investigate the long-term (52 wks) efficacy and safety of s.c. secukinumab in the MEASURE 2 study. <h3>Methods</h3> 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. <h3>Results</h3> 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 (<i>P</i>=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. <h3>Conclusions</h3> 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. <h3>References</h3> Sieper J, et al. Arthritis Rheumatol. 2014;66(11Suppl):S232 <h3>Acknowledgements</h3> Medical writing support was provided by Rachel Mason at Seren Communications (Tytherington, UK), and was funded by Novartis. <h3>Disclosure of Interest</h3> 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