Secukinumab shows sustained efficacy and low structural progression in ankylosing spondylitis: 4-year results from the MEASURE 1 study

Jürgen Braun, Xenofon Baraliakos, Atul Deodhar, Denis Poddubnyy, Paul Emery, Eumorphia M Delicha, Zsolt Talloczy, Brian Porter, Jürgen Braun, Xenofon Baraliakos, Atul Deodhar, Denis Poddubnyy, Paul Emery, Eumorphia M Delicha, Zsolt Talloczy, Brian Porter

Abstract

Objective: To evaluate the effect of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, on efficacy, imaging outcomes, and safety through 4 years (208 weeks) in patients with ankylosing spondylitis.

Methods: Patients opting to enrol had completed 2 years' treatment in the MEASURE 1 core study with subcutaneous secukinumab 150 or 75 mg every 4 weeks (q4Wk), following intravenous loading to Week (Wk) 4, or placebo treatment to Wk16/24. Up-titration from secukinumab 75-150 mg q4Wk was permitted following a protocol amendment. Efficacy is reported for patients originally randomized to secukinumab. Radiographic changes were assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and changes in MRI measures of inflammation using the Berlin scoring method. Safety and tolerability were evaluated.

Results: Among 274 extension study participants, 89.7% (78/87) and 93.0% (93/100) originally randomized to secukinumab 150 and 75 mg, respectively, completed 208Wk. Through Wk208, Assessment of Spondyloarthritis International Society 20/40 (observed) were 79.7%/60.8% (150 mg), 71.0%/43.5% (75 mg) and 80.0%/76% (up-titrators; n = 25). Mean (s.d.) changes in mSASSS were 1.2 (3.91) (150 mg), 1.8 (4.32) (75 mg) and 1.6 (5.67) (up-titrators). No radiographic progression (mSASSS change from Baseline < 2) was observed in 79% of patients receiving either secukinumab dose. Exposure-adjusted incidence rates per 100 patient-years were: serious infections (1.0), Candida infections (0.4), Crohn's disease (0.6), ulcerative colitis (0.2), and malignant/unspecified tumours (0.5), with no new safety signals.

Conclusion: Through 4 years, secukinumab provided sustained efficacy on signs and symptoms, and MRI outcomes, a low rate of radiographic progression and a consistent safety profile.

Trial registration: NCT01863732.

Keywords: MEASURE 1; ankylosing spondylitis; radiographic progression; secukinumab.

© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig . 1
Fig. 1
(A) ASAS20, (B) ASAS40 responses and (C) mean change from baseline in BASDAI through Wk208 Data are presented for patients originally randomized to secukinumab IV-150 mg. ASAS 20/40 are reported as observed and using multiple imputation. For BASDAI, mean change from baseline is reported as observed data and as least-square mean change (MMRM analysis). ASAS: Assessment of Spondyloarthritis International Society; IV: intravenous; MMRM: mixed model repeated measures; n: number of evaluable patients; N: total number of patients initially randomized to secukinumab 150 mg at baseline; Obs: observed data; Wk: week.
Fig . 2
Fig. 2
Cumulative probability plot for change from baseline in the mSASSS through Wk208 *Includes 23 patients whose dose was up-titrated from secukinumab 75 mg to 150 mg at various timepoints starting at Wk168, in accordance with a protocol amendment at the discretion of investigators. Data shown as observed. mSASSS: modified Stoke Ankylosing Spondylitis Spine Score; IV: intravenous; n: number of patients with evaluable paired X-rays at Baseline and Wk208; Wk: week.
Fig . 3
Fig. 3
Change in mSASSS between (A) Baseline to Wk104, (B) Wk104 to Wk208, (C) Baseline to Wk208 *Includes 23 patients (22 patients of whom had X-ray data at baseline, Wk104 and Wk208) whose dose was up-titrated from secukinumab 75 mg to 150 mg at various timepoints starting at Wk168. mSASSS score ranges from 0–72; higher scores indicate greater radiographic damage. Δ represents mean (s.d.) difference in mSASSS between timepoints. Baseline and Wk104 X-rays were re-read with Wk208 X-rays to minimize longitudinal variability. BL: baseline; IV: intravenous; mSASSS: modified Stoke Ankylosing Spondylitis Spine Score; n: number of patients with assessments at both timepoints; Wk: week.

References

    1. Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007;369:1379–90.
    1. Baraliakos X, Listing J, Rudwaleit M et al. . Progression of radiographic damage in patients with ankylosing spondylitis: defining the central role of syndesmophytes. Ann Rheum Dis 2007;66:910–5.
    1. Ramiro S, van der Heijde D, van Tubergen A et al. . Higher disease activity leads to more structural damage in the spine in ankylosing spondylitis: 12-year longitudinal data from the OASIS cohort. Ann Rheum Dis 2014;73:1455–61.
    1. Baraliakos X, Listing J, von der Recke A, Braun J. The natural course of radiographic progression in ankylosing spondylitis–evidence for major individual variations in a large proportion of patients. J Rheumatol 2009;36:997–1002.
    1. Maas F, Spoorenberg A, Brouwer E et al. . Spinal radiographic progression in patients with ankylosing spondylitis treated with TNF-a blocking therapy: a prospective longitudinal observational cohort study. PLoS One 2015;10:e0122693.
    1. Landewe R, Dougados M, Mielants H, van der Tempel H, van der Heijde D. Physical function in ankylosing spondylitis is independently determined by both disease activity and radiographic damage of the spine. Ann Rheum Dis 2009;68:863–7.
    1. Yang X, Fan D, Xia Q et al. . The health-related quality of life of ankylosing spondylitis patients assessed by SF-36: a systematic review and meta-analysis. Qual Life Res 2016;25:2711–23.
    1. van der Heijde D, Ramiro S, Landewe R et al. . 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 2017;76:978–91.
    1. Ward MM, Deodhar A, Akl EA et al. . American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Care Res 2016;68:151–66.
    1. Braun J, Baraliakos X, Deodhar A et al. . Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study. Ann Rheum Dis 2017;76:1070–7.
    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.
    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. Baeten D, Sieper J, Braun J et al. . Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med 2015;373:2534–48.
    1. Garrett S, Jenkinson T, Kennedy LG et al. . A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994;21:2286–91.
    1. Creemers MC, Franssen MJ, van’t Hof MA et al. . Assessment of outcome in ankylosing spondylitis: an extended radiographic scoring system. Ann Rheum Dis 2005;64:127–9.
    1. Bartelds GM, Krieckaert CL, Nurmohamed MT et al. . Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA 2011;305:1460–8.
    1. Vincent FB, Morand EF, Murphy K et al. . Antidrug antibodies (ADAb) to tumour necrosis factor (TNF)-specific neutralising agents in chronic inflammatory diseases: a real issue, a clinical perspective. Ann Rheum Dis 2013;72:165–78.
    1. Reich K, Blauvelt A, Armstrong A et al. . Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits minimal immunogenicity in patients with moderate-to-severe plaque psoriasis. Br J Dermatol 2017;176:752–8.
    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.
    1. Braun J, Baraliakos X, Hermann KG et al. . The effect of two golimumab doses on radiographic progression in ankylosing spondylitis: results through 4 years of the GO-RAISE trial. Ann Rheum Dis 2014;73:1107–13.
    1. van der Heijde D, Landewe R, Einstein S et al. . Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 2008;58:1324–31.
    1. van der Heijde D, Landewe R, Baraliakos X et al. . Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum 2008;58:3063–70.
    1. van der Heijde D, Salonen D, Weissman BN et al. . Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther 2009;11:R127.
    1. van der Heijde D, Baraliakos X, Hermann KA et al. . Limited radiographic progression and sustained reductions in MRI inflammation in patients with axial spondyloarthritis: 4-year imaging outcomes from the RAPID-axSpA phase III randomised trial. Ann Rheum Dis 2018;77:699–705.
    1. Maas F, Arends S, Brouwer E et al. . Reduction in spinal radiographic progression in ankylosing spondylitis patients receiving prolonged treatment with tumor necrosis factor inhibitors. Arthritis Care Res (Hoboken) 2017;69:1011–9.
    1. Haroon N, Inman RD, Learch TJ et al. . The impact of tumor necrosis factor alpha inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum 2013;65:2645–54.
    1. Marzo-Ortega H, McGonagle D, O’Connor P, Emery P. Efficacy of etanercept in the treatment of the entheseal pathology in resistant spondylarthropathy: a clinical and magnetic resonance imaging study. Arthritis Rheum 2001;44:2112–7.
    1. Wendling D, Joshi A, Reilly P et al. . 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.
    1. 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. Ann Rheum Dis 2018;77:999.

Source: PubMed

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