THU0210 Secukinumab Efficacy in Anti-Tnf-Naive Patients and Patients Previously Exposed to Anti-Tnf Therapy: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study (Measure 2) in Active Ankylosing Spondylitis
Authors: J. Sieper, J. Braun, X. Baraliakos, D.L. Baeten, M. Dougados, P. Emery, A. Deodhar, B. Porter, M. Andersson, H. Richards
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Current treatment options for ankylosing spondylitis (AS) patients with intolerance or an inadequate response to tumor necrosis factor alpha inhibitors (anti-TNF) are limited. Secukinumab, a human anti–interleukin-17A monoclonal antibody, significantly improved the signs and symptoms of AS in the phase 3 MEASURE 2 study (NCT01649375).<sup>1</sup> <h3>Objectives</h3> To evaluate the efficacy and safety of secukinumab by anti-TNF history in the MEASURE 2 study. <h3>Methods</h3> 219 adults with active AS were randomized to receive subcutaneous (s.c.) secukinumab (150 or 75 mg) or PBO at baseline, Wk 1, 2 and 3, and every 4 wks starting at Wk 4. Randomization was stratified according to prior anti-TNF experience: anti-TNF-naive, or inadequate response or intolerance to not more than one anti-TNF biologic agent (anti-TNF-IR). At Wk 16, PBO-treated subjects were re-randomized to secukinumab 150 or 75 mg. Pre-planned subgroup analyses of the primary and secondary endpoints were conducted among anti-TNF-naive and anti-TNF-IR subjects and included: the proportion of subjects achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 response (primary endpoint), ASAS40, high sensitivity C-reactive protein (hsCRP), ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Short Form-36 (SF-36), Ankylosing Spondylitis Quality of Life (ASQoL), and ASAS partial remission. Analyses at Wk 16 used non-responder imputation (for binary variables) and mixed-effects repeated measures model (for continuous variables). Wk 52 data are as observed. <h3>Results</h3> 62% of subjects enrolled were anti-TNF-naive and 38% were anti-TNF-IR. At Wk 16, secukinumab 150 mg (but not 75 mg) improved ASAS20 response rates compared with PBO in both anti-TNF-naive (68.2% vs 31.1%, respectively; <i>P</i>&lt;0.001) and anti-TNF-IR (50.0% vs 24.1%; <i>P</i>&lt;0.05) subjects. Improvements with secukinumab 150 mg were observed for all secondary endpoints in anti-TNF-naive subjects, except ASAS partial remission, and for most secondary endpoints in anti-TNF-IR subjects (Table). Clinical responses to secukinumab were sustained or continued to improve in both anti-TNF-naive and anti-TNF-IR subjects through 52 wks of therapy (Table). <h3>Conclusions</h3> Secukinumab 150 mg s.c. provided sustained improvement in the signs and symptoms of AS, with associated reduction in inflammation and improvement in physical function and health-related QoL in both anti-TNF-naive and anti-TNF-IR subjects. <h3>References</h3> Sieper J, et al. Arthritis Rheumatol. 2014;66(11 Suppl):S232. <h3>Acknowledgements</h3> Medical writing support was provided by Jessica Breen 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, B. Porter Shareholder of: Novartis, Employee of: Novartis, M. Andersson Employee of: Novartis, H. Richards Employee of: Novartis