BACKGROUND: Secukinumab, an anti-interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) in two phase 3 studies (MEASURE 1 and MEASURE 2). Here, we present 52-week results from the MEASURE 3 study assessing the efficacy and safety of secukinumab 300 and 150 mg subcutaneous maintenance dosing, following an intravenous loading regimen. METHODS: A total of 226 patients were randomized to intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous secukinumab 300 mg (IV-300 mg) or 150 mg (IV-150 mg) every 4 weeks, or matched placebo. Patients in the placebo group were re-randomized to subcutaneous secukinumab at a dose of 300 or 150 mg at week 16. The primary endpoint was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16 in the IV-300 mg or IV-150 mg versus placebo. Other endpoints assessed through week 52 included improvements in ASAS40, ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index, and ASAS partial remission responses, as well as the change from baseline in high-sensitivity C-reactive protein levels. Statistical analyses followed a predefined hierarchical hypothesis testing strategy to adjust for multiplicity of testing, with non-responder imputation used for binary variables and mixed-model repeated measures for continuous variables. RESULTS: The primary efficacy endpoint was met; the ASAS20 response rate was significantly greater at week 16 in the IV-300 mg (60.5%; P < 0.01) and IV-150 mg (58.1%; P < 0.05) groups versus placebo (36.8%). All secondary endpoints were met at week 16, except ASAS partial remission in the IV-150 mg group. Improvements achieved with secukinumab in all clinical endpoints at week 16 were also sustained at week 52. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period. During the entire treatment period, pooled incidence rates of Candida infections and grade 3-4 neutropenia were 1.8% for both of these adverse events in secukinumab-treated patients. CONCLUSIONS: Secukinumab (300 mg and 150 mg dose groups) provided rapid, significant and sustained improvement through 52 weeks in the signs and symptoms of patients with AS. The safety profile was consistent with previous reports, with no new or unexpected findings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02008916 . Registered on 8 December 2013. EUDRACT 2013-001090-24. Registered on 24 October 2013). The study was not retrospectively registered.

Altoona Center for Clinical Research Duncansville PA USA

Barts Health NHS Trust London UK

Centro de Investigación de Tratamientos Innovadores de Sinaloa Culiacán México

Division of Rheumatology Hospital Universitario Marqués de Valdecilla Santander Spain

Institute of Rheumatology and Department of Rheumatology 1st Faculty of Medicine Charles University Prague Czech Republic

Medical Plus s r o Uherske Hradiste Czech Republic

Novartis Pharma AG Basel Switzerland

Novartis Pharmaceuticals Corporation East Hanover NJ USA

Zobrazit více v PubMed

Dougados M, Baeten D. Spondyloarthritis. Lancet. 2011;377(9783):2127–37. doi: 10.1016/S0140-6736(11)60071-8. PubMed DOI

Garg N, van den Bosch F, Deodhar A. The concept of spondyloarthritis: where are we now? Best Pract Res Clin Rheumatol. 2014;28(5):663–72. doi: 10.1016/j.berh.2014.10.007. PubMed DOI

Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369(9570):1379–90. doi: 10.1016/S0140-6736(07)60635-7. PubMed DOI

Kotsis K, Voulgari PV, Drosos AA, Carvalho AF, Hyphantis T. Health-related quality of life in patients with ankylosing spondylitis: a comprehensive review. Expert Rev Pharmacoecon Outcomes Res. 2014;14(6):857–72. doi: 10.1586/14737167.2014.957679. PubMed DOI

Boonen A, van der Linden SM. The burden of ankylosing spondylitis. J Rheumatol Suppl. 2006;78:4–11. PubMed

Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD, Macfarlane GJ. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford) 2014;53(4):650–7. doi: 10.1093/rheumatology/ket387. PubMed DOI

Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, Dagfinrud H, Dijkmans B, Dougados M, Emery P, et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2011;70(6):896–904. doi: 10.1136/ard.2011.151027. PubMed DOI PMC

van der Heijde D, Schiff MH, Sieper J, Kivitz AJ, Wong RL, Kupper H, Dijkmans BA, Mease PJ, Davis JC., Jr 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(6):922–9. doi: 10.1136/ard.2007.087270. PubMed DOI PMC

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):1–14. doi: 10.1517/14728214.2015.993378. PubMed DOI

Sieper J. Treatment challenges in axial spondylarthritis and future directions. Curr Rheumatol Rep. 2013;15(9):356. doi: 10.1007/s11926-013-0356-9. PubMed DOI

Van Lümig PPM, Lecluse LLA, Driessen RJB, Spuls PI, Boezeman JB, Van De Kerkhof PCM, De Jong EMGJ. Switching from etanercept to adalimumab is effective and safe: results in 30 patients with psoriasis with primary failure, secondary failure or intolerance to etanercept. Br J Dermatol. 2010;163(4):838–46. doi: 10.1111/j.1365-2133.2010.09950.x. PubMed DOI

Lubberts E. The IL-23-IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol. 2015;11(7):415–29. doi: 10.1038/nrrheum.2015.53. PubMed DOI

Duarte JH. Spondyloarthropathies: IL-17A blockade ameliorates ankylosing spondylitis. Nat Rev Rheumatol. 2016;12(2):72. doi: 10.1038/nrrheum.2016.7. PubMed DOI

Baeten D, Baraliakos X, Braun J, Sieper J, Emery P, van der Heijde D, McInnes I, van Laar JM, Landewe R, Wordsworth P, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;382(9906):1705–13. doi: 10.1016/S0140-6736(13)61134-4. PubMed DOI

Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, Deodhar A, Porter B, Martin R, Andersson M, et al. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med. 2015;373(26):2534–48. doi: 10.1056/NEJMoa1505066. PubMed DOI

Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, Puig L, Nakagawa H, Spelman L, Sigurgeirsson B, et al. Secukinumab in plaque psoriasis–results of two phase 3 trials. N Engl J Med. 2014;371(4):326–38. doi: 10.1056/NEJMoa1314258. PubMed DOI

McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, van der Heijde D, Landewe R, Conaghan PG, Gottlieb AB, 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(9999):1137–46. doi: 10.1016/S0140-6736(15)61134-5. PubMed DOI

Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, Landewe R, Nash P, Pricop L, Yuan J, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373(14):1329–39. doi: 10.1056/NEJMoa1412679. PubMed DOI

McInnes IB, Sieper J, Braun J, Emery P, van der Heijde D, Isaacs JD, Dahmen G, Wollenhaupt J, Schulze-Koops H, Kogan J, et al. Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial. Ann Rheum Dis. 2014;73(2):349–56. doi: 10.1136/annrheumdis-2012-202646. PubMed DOI

Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH, Durez P, et al. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med. 2010;2:52ra72. doi: 10.1126/scitranslmed.3001107. PubMed DOI

Gottlieb AB, Blauvelt A, Prinz JC, Papanastasiou P, Pathan R, Nyirady J, Fox T, Papavassilis C. Secukinumab self-administration by prefilled syringe maintains reduction of plaque psoriasis severity over 52 weeks: results of the FEATURE trial. J Drugs Dermatol. 2016;15(10):1226–34. PubMed

Van den Bosch F, Deodhar A. Treatment of spondyloarthritis beyond TNF-alpha blockade. Best Pract Res Clin Rheumatol. 2014;28(5):819–27. doi: 10.1016/j.berh.2014.10.019. PubMed DOI

Filler SG, Yeaman MR, Sheppard DC. Tumor necrosis factor inhibition and invasive fungal infections. Clin Infect Dis. 2005;41(Suppl 3):S208–12. doi: 10.1086/430000. PubMed DOI

Perez-Alvarez R, Perez-de-Lis M, Ramos-Casals M. Biologics-induced autoimmune diseases. Curr Opin Rheumatol. 2013;25(1):56–64. doi: 10.1097/BOR.0b013e32835b1366. PubMed DOI

Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum. 2007;56(9):2886–95. doi: 10.1002/art.22864. PubMed DOI

Ottaviani S, Cerf-Payrastre I, Kemiche F, Pertuiset E. Adalimumab-induced neutropenia in a patient with rheumatoid arthritis. Joint Bone Spine. 2009;76(3):312–3. doi: 10.1016/j.jbspin.2008.09.017. PubMed DOI

HUMIRA: Highlights of prescribing information. [http://www.rxabbvie.com/pdf/humira.pdf]. Accessed 21 Nov 2016.

ENBREL: Highlights of prescribing information. [http://pi.amgen.com/united_states/enbrel/derm/enbrel_pi.pdf]. Accessed 21 Nov 2016.

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

Nonsteroidal anti-inflammatory drug-sparing effect of secukinumab in patients with radiographic axial spondyloarthritis: 4-year results from the MEASURE 2, 3 and 4 phase III trials

A Pooled Analysis Reporting the Efficacy and Safety of Secukinumab in Male and Female Patients with Ankylosing Spondylitis

Improvement of Signs and Symptoms of Nonradiographic Axial Spondyloarthritis in Patients Treated With Secukinumab: Primary Results of a Randomized, Placebo-Controlled Phase III Study

Drug retention, inactive disease and response rates in 1860 patients with axial spondyloarthritis initiating secukinumab treatment: routine care data from 13 registries in the EuroSpA collaboration

Secukinumab 150/300 mg Provides Sustained Improvements in the Signs and Symptoms of Active Ankylosing Spondylitis: 3-Year Results from the Phase 3 MEASURE 3 Study

Efficacy and Safety of Secukinumab 150 mg with and Without Loading Regimen in Ankylosing Spondylitis: 104-week Results from MEASURE 4 Study

Zobrazit více v PubMed

ClinicalTrials.gov
NCT02008916

EudraCT
2013-001090-24