OBJECTIVE: To report the primary (1-year) results from PREVENT, the first phase III study evaluating secukinumab in patients with active nonradiographic axial spondyloarthritis (SpA). METHODS: A total of 555 patients were randomized (1:1:1) to receive subcutaneous secukinumab 150 mg with a loading dose (loading dose [LD] group), secukinumab 150 mg without a loading dose (non-loading dose [NL] group), or placebo weekly and then every 4 weeks starting at week 4. The NL group received placebo at weeks 1, 2, and 3 to maintain blinding. Switch to open-label secukinumab or standard of care was permitted after week 20. The study had 2 independent analysis plans, per European Union and non-US (plan A; week 16) and US (plan B; week 52) regulatory requirements. The primary end point was 40% improvement in disease activity according to the Assessment of SpondyloArthritis international Society (ASAS40) criteria at week 16 (in the LD group) and at week 52 (in the NL group) in tumor necrosis factor inhibitor (TNFi)-naive patients. Safety analyses included all patients who received ≥1 dose of study treatment. RESULTS: Overall, 481 patients completed 52 weeks of treatment, including 84.3% (156 of 185) in the LD group, 89.7% (165 of 184) in the NL group, and 86.0% (160 of 186) in the placebo group. The proportion of patients who switched to open-label or standard of care between weeks 20 and 48 was 50.8% in the LD group, 47.3% in the NL group, and 64.0% in the placebo group. Both primary and all secondary end points were met at week 16. The proportion of TNFi-naive patients who met ASAS40 was significantly higher for LD at week 16 (41.5%) and NL at week 52 (39.8%) versus placebo (29.2% at week 16 and 19.9% at week 52; both P < 0.05). No new safety findings were reported. CONCLUSION: Our findings indicate that secukinumab 150 mg provides significant and sustained improvement in signs and symptoms of nonradiographic axial SpA through 52 weeks. Safety was consistent with previous reports.

Altoona Center for Clinical Research Duncansville Pennsylvania

Amsterdam UMC University of Amsterdam Amsterdam Rheumatology and Immunology Center Amsterdam The Netherlands

Charité Universitätsmedizin Berlin Germany

Hospital University Marqués de Valdecilla IDIVAL Santander Spain

Medical Plus s r o Uherské Hradiště Czech Republic University of Veterinary and Pharmaceutical Sciences Brno Czech Republic

Monash University Melbourne Victoria Australia

Novartis East Hanover New Jersey

Novartis Pharma AG Basel Switzerland

Oregon Health and Science University Portland

Rheumazentrum Ruhrgebiet Herne Germany and Ruhr University Bochum Bochum Germany

Toho University Tokyo Japan

Zobrazit více v PubMed

Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet 2017;390:73–84. PubMed

Sieper J, Braun J, Dougados M, Baeten D. Axial spondyloarthritis [review]. Nat Rev Dis Primers 2015;1:15013. PubMed

Deodhar A, Strand V, Kay J, Braun J. The term ‘non‐radiographic axial spondyloarthritis’ is much more important to classify than to diagnose patients with axial spondyloarthritis. Ann Rheum Dis 2016;75:791–4. PubMed

Lockwood MM, Gensler LS. Nonradiographic axial spondyloarthritis. Best Pract Res Clin Rheumatol 2017;31:816–29. PubMed

Wang R, Ward MM. Epidemiology of axial spondyloarthritis: an update. Curr Opin Rheumatol 2018;30:137–43. PubMed PMC

Malaviya AN, Rawat R, Agrawal N, Patil NS. The nonradiographic axial spondyloarthritis, the radiographic axial spondyloarthritis, and ankylosing spondylitis: the tangled skein of rheumatology [review]. Int J Rheumatol 2017;2017:1824794. PubMed PMC

Burgos‐Varga R, Wei JC, Rahman MU, Akkoc N, Haq SA, Hammoudeh M, et al. The prevalence and clinical characteristics of nonradiographic axial spondyloarthritis among patients with inflammatory back pain in rheumatology practices: a multinational, multicenter study. Arthritis Res Ther 2016;18:132. PubMed PMC

Poddubnyy D, Rudwaleit M. Early spondyloarthritis. Rheum Dis Clin North Am 2012;38:387–403. PubMed

Reveille JD, Weisman MH. The epidemiology of back pain, axial spondyloarthritis and HLA‐B27 in the United States. Am J Med Sci 2013;345:431–6. PubMed PMC

Protopopov M, Poddubnyy D. Radiographic progression in nonradiographic axial spondyloarthritis. Expert Rev Clin Immunol 2018;14:525–33. PubMed

Redeker I, Callhoff J, Hoffmann F, Haibel H, Sieper J, Zink A, et al. Determinants of diagnostic delay in axial spondyloarthritis: an analysis based on linked claims and patient‐reported survey data. Rheumatology (Oxford) 2019;58:1634–8. PubMed

Sykes MP, Doll H, Sengupta R, Gaffney K. Delay to diagnosis in axial spondyloarthritis: are we improving in the UK? Rheumatology (Oxford) 2015;54:2283–4. PubMed

Poddubnyy D, Rudwaleit M, Haibel H, Listing J, Marker‐Hermann E, Zeidler H, et al. Rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial spondyloarthritis. Ann Rheum Dis 2011;70:1369–74. PubMed

Van der Heijde D, Ramiro S, Landewe R, Baraliakos X, van den Bosch F, Sepriano A, et al. 2016 update of the ASAS‐EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 2017;76:978–91. PubMed

Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, et al. 2019 update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol 2019;71:1599–613. PubMed PMC

Robinson PC, Sengupta R, Siebert S. Nonradiographic axial spondyloarthritis (nr‐axSpA): advances in classification, imaging and therapy. Rheumatol Ther 2019;6:165–77. PubMed PMC

Miossec P, Korn T, Kuchroo VK. Interleukin‐17 and type 17 helper T cells. N Engl J Med 2009;361:888–98. 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

Baraliakos X, Deodhar A, Poddubnyy D, Kivitz A, Tahir H, van den Bosch F, et al. Long‐term efficacy and safety of secukinumab 150 mg in ankylosing spondylitis: 5‐year results from the phase III MEASURE 1 extension study. RMD Open 2019;5:e001005. PubMed PMC

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

Rudwaleit M, Jurik AG, Hermann KG, Landewé R, van der Heijde D, Baraliakos X, et al. Defining active sacroiliitis on magnetic resonance imaging (MRI) for classification of axial spondyloarthritis: a consensual approach by the ASAS/OMERACT MRI group. Ann Rheum Dis 2009;68:1520–7. PubMed

Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis: a proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361–8. PubMed

World Medical Association . World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013;310:2191–4. PubMed

Sieper J, Rudwaleit M, Baraliakos X, Brandt J, Braun J, Burgos‐Vargas R, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis 2009;68:ii1–44. PubMed

Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994;21:2286–91. PubMed

Ware JE Jr. SF‐36 health survey update. Spine (Phila Pa 1976) 2000;25:3130–9. PubMed

Doward LC, Spoorenberg A, Cook SA, Whalley D, Helliwell PS, Kay LJ, et al. Development of the ASQoL: a quality of life instrument specific to ankylosing spondylitis. Ann Rheum Dis 2003;62:20–6. PubMed PMC

Lukas C, Landewe R, Sieper J, Dougados M, Davis J, Braun J, et al. Development of an ASAS‐endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009;68:18–24. PubMed

Sieper J, van der Heijde D, Dougados M, Mease PJ, Maksymowych WP, Brown MA, et al. Efficacy and safety of adalimumab in patients with nonradiographic axial spondyloarthritis: results of a randomised placebo‐controlled trial (ABILITY‐1). Ann Rheum Dis 2013;72:815–22. PubMed PMC

Sieper J, van der Heijde D, Dougados M, Maksymowych WP, Scott BB, Boice JA, et al. A randomized, double‐blind, placebo‐controlled, sixteen‐week study of subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis. Arthritis Rheumatol 2015;67:2702–12. PubMed PMC

Dougados M, van der Heijde D, Sieper J, Braun J, Maksymowych WP, Citera G, et al. Symptomatic efficacy of etanercept and its effects on objective signs of inflammation in early nonradiographic axial spondyloarthritis: a multicenter, randomized, double‐blind, placebo‐controlled trial. Arthritis Rheumatol 2014;66:2091–102. PubMed

Deodhar A, Gensler LS, Kay J, Maksymowych WP, Haroon N, Landewé R, et al. A fifty‐two–week, randomized, placebo‐controlled trial of certolizumab pegol in nonradiographic axial spondyloarthritis. Arthritis Rheumatol 2019;71:1101–11. PubMed PMC

Deodhar A, van der Heijde D, Gensler LS, Kim TH, Maksymowych WP, Ostergaard M, et al. Ixekizumab for patients with nonradiographic axial spondyloarthritis (COAST‐X): a randomised, placebo‐controlled trial. Lancet 2020;395:53–64. PubMed

Deodhar A, Mease PJ, McInnes IB, Baraliakos X, Reich K, Blauvelt A, et al. Long‐term safety of secukinumab in patients with moderate‐to‐severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post‐marketing surveillance data. Arthritis Res Ther 2019;21:111. PubMed PMC

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

Efficacy and safety of secukinumab in patients with spondyloarthritis and enthesitis at the Achilles tendon: results from a phase 3b trial

Zobrazit více v PubMed

ClinicalTrials.gov
NCT02696031