OBJECTIVE: Secukinumab 150 mg has demonstrated significant improvement in signs and symptoms of ankylosing spondylitis (AS), with response rates sustained for up to 5 years. Here, we report end-of-study 3-year efficacy and safety results of secukinumab 150 and 300 mg from the MEASURE 3 study. METHODS: A total of 226 patients was randomized to intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous (s.c.) secukinumab 300/150 mg every 4 weeks or a matched placebo. At week 16, placebo patients were re-randomized to s.c. secukinumab 300/150 mg. Analysis at week 156 included patients initially randomized to secukinumab and those who switched from placebo to secukinumab at week 16 (any secukinumab 300/150 mg). Outcome measures at week 156 included Assessment of Spondyloarthritis International Society (ASAS) 20/40, Bath Ankylosing Spondylitis Disease Activity Index, ASAS partial remission (PR), ASAS 5/6, and Ankylosing Spondylitis Disease Activity Score-C-reactive protein inactive disease. RESULTS: The retention rates from weeks 16 to 156 were 80.5% and 80.9% in secukinumab 300 and 150 mg, respectively. ASAS 20/40 response rates at week 156 were 75.0%/56.5% and 68.2%/47.7% for secukinumab 300 and 150 mg, respectively. At week 156, response rates on more stringent clinical end points (eg, ASAS 40, ASAS-PR) were higher with the 300-mg dose, particularly in tumor necrosis factor (TNF)-inadequate responder (IR) patients. No new safety findings were observed. CONCLUSION: Secukinumab (300 and 150 mg) provided sustained improvements through 3 years in the signs and symptoms of active AS. Improvements with secukinumab 300 mg were numerically higher compared with the 150-mg dose for some higher hurdle end points and in TNF-IR patients. The safety profile of secukinumab was consistent with previous reports.

Altoona Center for Clinical Research Duncansville Pennsylvania

Barts Health National Health Service Trust London UK

Centro de Investigación de Tratamientos Innovadores de Sinaloa Culiacán México

Charles University Prague Czech Republic

Hospital Universitario Marqués de Valdecilla Santander Spain

Medical Plus s r o Uherske Hradiste and University of Veterinary and Pharmaceutical Sciences Brno Czech Republic

Novartis Ireland Limited Dublin Ireland

Novartis Pharma AG Basel Switzerland

Novartis Pharmaceuticals Corporation East Hanover New Jersey

See more in PubMed

Dougados M, Baeten D. Spondyloarthritis. Lancet 2011;377:2127–37. PubMed

Braun J, Kiltz U, Heldmann F, Baraliakos X. Emerging drugs for the treatment of axial and peripheral spondyloarthritis. Expert Opin Emerg Drugs 2015;20:1–14. PubMed

Van der Heijde D, Schiff MH, Sieper J, Kivitz AJ, Wong RL, Kupper H, et al. Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long‐term results from the ATLAS trial. Ann Rheum Dis 2009;68:922–9. PubMed PMC

Lie E, van der Heijde D, Uhlig T, Mikkelson K, Rødevand E, Koldingsnes W, et al. Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR‐DMARD register. Ann Rheum Dis 2011;70:157–63. PubMed

Song IH, Heldmann F, Rudwaleit M, Listing J, Appel H, Braun J, et al. Different response to rituximab in tumor necrosis factor blocker‐naive patients with active ankylosing spondylitis and in patients in whom tumor necrosis factor blockers have failed: a twenty‐four‐week clinical trial. Arthritis Rheum 2010;62:1290–7. PubMed

Sepriano A, Regel A, van der Heijde D, Braun J, Baraliakos X, Landewé R, et al. Efficacy and safety of biological and targeted‐synthetic DMARDs: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. RMD Open 2017;3:e000396. PubMed PMC

Smolen JS, Schöls M, Braun J, Dougados M, FitzGerald O, Gladman DD, et al. Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. Ann Rheum Dis 2018;77:3–17. PubMed PMC

Lubberts E. The IL‐23‐IL‐17 axis in inflammatory arthritis. Nat Rev Rheumatol 2015;11:415–29. PubMed

Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, et al. Secukinumab, an interleukin‐17A inhibitor, in ankylosing spondylitis. N Engl J Med 2015;373:2534–48. PubMed

Pavelka K, Kivitz A, Dokoupilova E, Blanco R, Maradiaga M, Tahir H, et al. Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double‐blind phase 3 study, MEASURE 3. Arthritis Res Ther 2017;19:285. PubMed PMC

Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, et al. Secukinumab in plaque psoriasis–results of two phase 3 trials. N Engl J Med 2014;371:326–38. PubMed

McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, et al. Secukinumab, a human anti‐interleukin‐17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double‐blind, placebo‐controlled, phase 3 trial. Lancet 2015;386:1137–46. PubMed

Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, et al. Secukinumab inhibition of interleukin‐17A in patients with psoriatic arthritis. N Engl J Med 2015;373:1329–39. PubMed

Nash P, Mease PJ, McInnes IB, Rahman P, Ritchlin CT, Blanco R, et al. Efficacy and safety of secukinumab administration by autoinjector in patients with psoriatic arthritis: results from a randomized, placebo‐controlled trial (FUTURE 3). Arthritis Res Ther 2018;20:47. PubMed PMC

Schreiber S, Colombel JF, Feagan BG, Reich K, Deodhar AA, McInnes IB, et al. Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials. Ann Rheum Dis 2019;78:473–9. PubMed PMC

Wendling D, Joshi A, Reilly P, Jalundhwala YJ, Mittal M, Bao Y. Comparing the risk of developing uveitis in patients initiating anti‐tumor necrosis factor therapy for ankylosing spondylitis: an analysis of a large US claims database. Curr Med Res Opin 2014;30:2515–21. PubMed

Deodhar A, Miceli‐Richard C, Baraliakos X, et al. Low incidence of both new‐onset and flares of uveitis in secukinumab‐treated patients with ankylosing spondylitis: clinical trial and post‐marketing safety analysis [abstract]. Ann Rheum Dis 2018;70 Suppl 10 URL: https://acrabstracts.org/abstract/low-incidence-of-both-new-onset-and-flares-of-uveitis-in-secukinumab-treated-patients-with-ankylosing-spondylitis-clinical-trial-and-post-marketing-safety-analysis/.

Efficacy and Safety of Intravenous Secukinumab in Patients With Active Axial Spondyloarthritis: Results From a Randomized, Placebo-Controlled, Phase 3 Study