Treat-to-target strategy with secukinumab as a first-line biological disease modifying anti-rheumatic drug compared to standard-of-care treatment in patients with active axial spondyloarthritis: protocol for a randomised open-label phase III study, AScalate

Denis Poddubnyy, Ludwig Hammel, Marvin Heyne, Justyna Veit, Claudia Jentzsch, Xenofon Baraliakos, Denis Poddubnyy, Ludwig Hammel, Marvin Heyne, Justyna Veit, Claudia Jentzsch, Xenofon Baraliakos

Abstract

Introduction: In patients with axial spondyloarthritis (axSpA), biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended to those with inadequate response or contraindications to non-steroidal anti-inflammatory drugs (NSAIDs). In case of failure of the first bDMARD, a switch within the class or to other bDMARD is recommended. Despite these treatment options, there is no optimal treat-to-target (T2T) strategy. This study aims to evaluate the efficacy of a T2T strategy in patients with axSpA, with secukinumab as a first-line bDMARD, compared with standard-of-care (SOC) treatment.

Methods and analyses: This is a randomised, parallel-group, open-label, multicentre ongoing study in patients with axSpA who are naïve to bDMARD and who have had an inadequate response to NSAIDs. The study will include an 8-week screening period, a 36-week treatment period and a 20-week safety follow-up period. At baseline, patients will be randomised (1:1) to T2T or SOC group. In the T2T group, patients will be treated with secukinumab 150 mg subcutaneous (s.c.) weekly until week 4 and then at week 8. For non-responders (patients without Ankylosing Spondylitis Disease Activity Score [ASDAS] clinically important improvement; change from baseline ≥1.1) at week 12, dose will be escalated to 300 mg s.c. every 4 weeks until week 24. Non-responders at week 24 will be switched to adalimumab biosimilar 40 mg s.c. every 2 weeks until week 34. In the SOC group, patients will receive treatment at the discretion of the physician. The primary endpoint is the proportion of patients achieving an Assessment in SpondyloArthritis International Society 40% (ASAS40) response at week 24.

Ethics and dissemination: The study is being conducted as per the ethical principles of the Declaration of Helsinki and after approval from independent ethics committees/institutional review boards. The first results are expected to be published in early 2022.

Trial registration number: This study is registered with ClinicalTrials.gov, NCT03906136.

Keywords: immunology; rheumatology.

Conflict of interest statement

Competing interests: DP reports grants and personal fees from Abbvie, Eli Lilly, MSD, Novartis, and Pfizer, personal fees from Roche, BMS, UCB, and Celgene, outside the submitted work. XB reports consulting fees, research or institutional support and educational grants from AbbVie, BMS, Celgene, Chugai, Galapagos, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, Sanofi and UCB. LH has no conflicts of interest to disclose. MH, JV and CJ are employees of Novartis Pharma GmbH.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study design. BSL, baseline; s.c., subcutaneous;SOC, standard-of-care.

References

    1. Rudwaleit M, van der Heijde D, Landewé R, et al. . The development of assessment of spondyloarthritis international society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009;68:777–83. 10.1136/ard.2009.108233
    1. Poddubnyy D, Sieper J. Similarities and differences between nonradiographic and radiographic axial spondyloarthritis: a clinical, epidemiological and therapeutic assessment. Curr Opin Rheumatol 2014;26:377–83. 10.1097/BOR.0000000000000071
    1. Baraliakos X, Braun J. Non-radiographic axial spondyloarthritis and ankylosing spondylitis: what are the similarities and differences? RMD Open 2015;1:e000053. 10.1136/rmdopen-2015-000053
    1. Poddubnyy D, Rudwaleit M, Haibel 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. 10.1136/ard.2010.145995
    1. Poddubnyy D, van Tubergen A, Landewé R, et al. . Development of an ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis. Ann Rheum Dis 2015;74:1483–7. 10.1136/annrheumdis-2014-207151
    1. Redeker I, Callhoff J, Hoffmann F, et al. . Determinants of diagnostic delay in axial spondyloarthritis: an analysis based on linked claims and patient-reported survey data. Rheumatology 2019;58:1634–8. 10.1093/rheumatology/kez090
    1. Rudwaleit M, Listing J, Brandt J, et al. . Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis. Ann Rheum Dis 2004;63:665–70. 10.1136/ard.2003.016386
    1. Sieper J, Lenaerts J, Wollenhaupt J, et al. . Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, part 1. Ann Rheum Dis 2014;73:101–7. 10.1136/annrheumdis-2012-203201
    1. Braun J, van den Berg R, Baraliakos X, et al. . 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2011;70:896–904. 10.1136/ard.2011.151027
    1. van der Heijde D, Ramiro S, Landewé R, et al. . 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 2017;76:978–91. 10.1136/annrheumdis-2016-210770
    1. van der Heijde D, Sieper J, Maksymowych WP, et al. . 2010 update of the International ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis. Ann Rheum Dis 2011;70:905–8. 10.1136/ard.2011.151563
    1. Marzo-Ortega H, Sieper J, Kivitz A, et al. . Secukinumab provides sustained improvements in the signs and symptoms of active ankylosing spondylitis with high retention rate: 3-year results from the phase III trial, measure 2. RMD Open 2017;3:e000592. 10.1136/rmdopen-2017-000592
    1. Marzo-Ortega H, Sieper J, Kivitz A, et al. . Secukinumab and sustained improvement in signs and symptoms of patients with active ankylosing spondylitis through two years: results from a phase III study. Arthritis Care Res 2017;69:1020–9. 10.1002/acr.23233
    1. Baeten D, Sieper J, Braun J, et al. . Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med 2015;373:2534–48. 10.1056/NEJMoa1505066
    1. Baraliakos X, Kivitz AJ, Deodhar AA, et al. . Long-term effects of interleukin-17A inhibition with secukinumab in active ankylosing spondylitis: 3-year efficacy and safety results from an extension of the phase 3 measure 1 trial. Clin Exp Rheumatol 2018;36:50–5.
    1. Baraliakos X, Berenbaum F, Favalli EG, et al. . Challenges and advances in targeting remission in axial spondyloarthritis. J Rheumatol 2018;45:153–7. 10.3899/jrheum.170222
    1. Smolen JS, Schöls M, Braun J, 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. 10.1136/annrheumdis-2017-211734
    1. Chan A-W, Tetzlaff JM, Altman DG, et al. . SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med 2013;158:200–7. 10.7326/0003-4819-158-3-201302050-00583
    1. Lukas C, Landewé R, Sieper J, et al. . Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009;68:18–24. 10.1136/ard.2008.094870
    1. Machado PM, Landewé R, Heijde Dvander, et al. . Ankylosing spondylitis disease activity score (ASDAS): 2018 update of the nomenclature for disease activity states. Ann Rheum Dis 2018;77:1539–40. 10.1136/annrheumdis-2018-213184
    1. Haywood KL, Garratt AM, Dawes PT. Patient-assessed health in ankylosing spondylitis: a structured review. Rheumatology 2005;44:577–86. 10.1093/rheumatology/keh549
    1. Jenkinson TR, Mallorie PA, Whitelock HC, et al. . Defining spinal mobility in ankylosing spondylitis (as). The Bath as Metrology index. J Rheumatol 1994;21:1694–8.
    1. Langley RG, Elewski BE, Lebwohl M, et al. . Secukinumab in plaque psoriasis-results of two phase 3 trials. N Engl J Med 2014;371:326–38. 10.1056/NEJMoa1314258
    1. Kiltz U, van der Heijde D, Boonen A, et al. . Development of a health index in patients with ankylosing spondylitis (ASAS HI): final result of a global initiative based on the ICF guided by ASAS. Ann Rheum Dis 2015;74:830–5. 10.1136/annrheumdis-2013-203967
    1. Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. conceptual framework and item selection. Med Care 1992;30:473–83.
    1. Doward LC, Spoorenberg A, Cook SA, et al. . Development of the ASQoL: a quality of life instrument specific to ankylosing spondylitis. Ann Rheum Dis 2003;62:20–6. 10.1136/ard.62.1.20
    1. Yellen SB, Cella DF, Webster K, et al. . Measuring fatigue and other anemia-related symptoms with the functional assessment of cancer therapy (fact) measurement system. J Pain Symptom Manage 1997;13:63–74. 10.1016/S0885-3924(96)00274-6
    1. Bauer P, Köhne K. Evaluation of experiments with adaptive interim analyses. Biometrics 1994;50:1029–41. 10.2307/2533441
    1. Glintborg B, Sørensen IJ, Østergaard M, et al. . Ankylosing spondylitis versus nonradiographic axial spondyloarthritis: comparison of tumor necrosis factor inhibitor effectiveness and effect of HLA-B27 status. An observational cohort study from the nationwide DANBIO registry. J Rheumatol 2017;44:59–69. 10.3899/jrheum.160958
    1. Moltó A, Paternotte S, Claudepierre P, et al. . Effectiveness of tumor necrosis factor α blockers in early axial spondyloarthritis: data from the DESIR cohort. Arthritis Rheumatol 2014;66:1734–44. 10.1002/art.38613
    1. Pavelka K, Kivitz A, Dokoupilova E, 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. 10.1186/s13075-017-1490-y
    1. Sieper J, Deodhar A, Marzo-Ortega H, et al. . Secukinumab efficacy in anti-TNF-naive and anti-TNF-experienced subjects with active ankylosing spondylitis: results from the measure 2 study. Ann Rheum Dis 2017;76:571–92. 10.1136/annrheumdis-2016-210023
    1. van der Heijde D, Kivitz A, Schiff MH, et al. . Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2006;54:2136–46. 10.1002/art.21913

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere