Background Secukinumab, an anti–interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) over 52 weeks (wks) in the randomised, double-blind, placebo (PBO)-controlled, Phase 3 MEASURE 2 study (NCT01649375).1
Objectives To evaluate the long-term (104 wks) efficacy and safety of secukinumab in MEASURE 2 study.
Methods 219 subjects with active AS, classified by modified New York criteria, despite therapy with NSAIDs, were randomised to subcutaneous (s.c.) secukinumab 150 or 75 mg or PBO at baseline (BL), Wks 1, 2 and 3, and every 4 wks (q4w) from Wk 4. At Wk 16, PBO-treated subjects were re-randomised to secukinumab 150 or 75 mg s.c. q4w. At BL, 39% of subjects had an inadequate response/intolerance to prior anti-TNF therapy (anti–TNF-IR). Primary endpoint was ASAS20 response rates at Wk 16. Secondary endpoints included ASAS40, hsCRP, ASAS5/6, BASDAI, SF-36 PCS and ASAS partial remission. Endpoints were assessed through Wk 104, with multiple imputation for binary variables and a mixed-model repeated measures for continuous variables. Analyses stratified by anti-TNF history were pre-specified and are reported as observed.
Results 60/72 (83.3%), 57/73 (78.1%) and 57/74 (77%) subjects completed 104 wks of treatment with secukinumab 150 mg, 75 mg and PBO, respectively. As reported previously, secukinumab 150 mg significantly improved all pre-specified endpoints at Wk 16 vs. PBO, except ASAS partial remission; the 75 mg dose did not reach statistical significance at Wk 16 based on hierarchical testing.1 ASAS20/40 response rates at Wk 104 were 71.5/47.5% with both secukinumab doses. Clinical improvements with secukinumab were sustained through Wk 104 across all secondary endpoints (Table). In the subgroup of anti–TNF-naïve subjects, ASAS20/40 response rates at Wk 104 (observed data) were 76.9/56.4% and 80.0/60.0% with secukinumab 150 mg and 75 mg, respectively; corresponding rates in anti–TNF-IR subjects were 85.0/50.0% and 68.8/43.8%. Across the treatment period (mean secukinumab exposure: 735.6 days), exposure-adjusted incidence rates for serious infections/infestations, IBD, malignant/unspecified tumours and MACE with secukinumab were 1.2, 1.4, 0.5 and 0.7 per 100 subject-years, respectively. No cases of TB, opportunistic infections or suicidality-related AEs were reported.
Conclusions Secukinumab provided sustained improvement through 2 years in the signs and symptoms of AS with improved physical function, regardless of anti-TNF status. Safety was consistent with previous reports.
Baeten D et al. N Engl J Med 2015;373:2534–48
Disclosure of Interest H. Marzo-Ortega Grant/research support from: Janssen and Pfizer, Consultant for: Abbvie, Celgene, Janssen, Novartis and UCB, Speakers bureau: Abbvie, Celgene, Janssen and UCB, C. Legerton Grant/research support from: AbbVie, Ablynx, Acerta, Amgen, AstraZeneca, Celgene, GSK, Janssen, E. Lilly, BMS, Pfizer, Novartis, Sandoz, UCB, Daiichi Sankyo, ChemoCentryx, Boehringer Ingelheim, Speakers bureau: Celgene and Amgen, 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, A. Kivitz Consultant for: AbbVie, Pfizer, Genentech, UCB and Celgene, Speakers bureau: Celgene, Pfizer, and Genentech, R. Blanco: None declared, M. Cohen Consultant for: Abbvie, Amgen, BMS, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB, J. Zuazo Employee of: Novartis, A. Readie Shareholder of: Novartis, Employee of: Novartis, B. Porter Shareholder of: Novartis, Employee of: Novartis, H. Richards Employee of: Novartis