Filgotinib decreases both vertebral body and posterolateral spine inflammation in ankylosing spondylitis: results from the TORTUGA trial

Walter P Maksymowych, Mikkel Østergaard, Robert Landewé, William Barchuk, Ke Liu, Leen Gilles, Thijs Hendrikx, Robin Besuyen, Xenofon Baraliakos, Walter P Maksymowych, Mikkel Østergaard, Robert Landewé, William Barchuk, Ke Liu, Leen Gilles, Thijs Hendrikx, Robin Besuyen, Xenofon Baraliakos

Abstract

Objectives: To assess the effects of filgotinib on inflammatory and structural changes at various spinal locations, based on MRI measures in patients with active AS in the TORTUGA trial.

Methods: In the TORTUGA trial, patients with AS received filgotinib 200 mg (n = 58) or placebo (n = 58) once daily for 12 weeks. In this post hoc analysis, spine MRIs were evaluated using the Canada-Denmark (CANDEN) MRI scoring system to assess changes from baseline to week 12 in total spine and subscores for inflammation, fat, erosion and new bone formation (NBF) at various anatomical locations. Correlations were assessed between CANDEN inflammation and clinical outcomes and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores and between baseline CANDEN NBF and baseline BASFI and BASMI scores.

Results: MRIs from 47 filgotinib- and 41 placebo-treated patients were evaluated. There were significantly larger reductions with filgotinib vs placebo in total spine inflammation score and most inflammation subscores, including posterolateral elements (costovertebral joints, transverse/spinous processes, soft tissues), facet joints and vertebral bodies. No significant differences were observed for corner or non-corner vertebral body inflammation subscores, spine fat lesion, bone erosion or NBF scores. In the filgotinib group, the change from baseline in the total inflammation score correlated positively with the SPARCC spine score. Baseline NBF scores correlated with baseline BASMI but not BASFI scores.

Conclusions: Compared with placebo, filgotinib treatment was associated with significant reductions in MRI measures of spinal inflammation, including in vertebral bodies, facet joints and posterolateral elements.

Trial registration: ClinicalTrials.gov (https://ichgcp.net/clinical-trials-registry/NCT03117270" title="See in ClinicalTrials.gov">NCT03117270.

Keywords: AS; MRI; filgotinib; inflammation; therapeutics.

© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig . 1
Fig. 1
Change from baseline in CANDEN MRI score: (A) total spine inflammation score, (B) vertebral body inflammation subscore, (C) posterior elements inflammation subscore, (D) posterolateral elements inflammation subscore, (E) facet joints inflammation subscore, (F) vertebral body corner inflammation subscore, and (G) vertebral body non-corner inflammation subscore
Fig . 2
Fig. 2
Short tau inversion recovery MRI at (A) baseline and (B) week 12 from a patient who had received filgotinib. MRI scans demonstrate posterolateral inflammation (top arrow), facet joint inflammation (middle two arrows) and soft-tissue inflammation (bottom arrow) in the lumbar spine that resolved after treatment

References

    1. Dubash S, McGonagle D, Marzo-Ortega H. New advances in the understanding and treatment of axial spondyloarthritis: from chance to choice. Ther Adv Chronic Dis 2018;9:77–87.
    1. Carli L, Calabresi E, Governato G, Braun J. One year in review 2018: axial spondyloarthritis. Clin Exp Rheumatol 2019;37:889–98.
    1. Taurog JD, Chhabra A, Colbert RA. Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med 2016;374:2563–74.
    1. Boel A, Molto A, van der Heijde D et al. Do patients with axial spondyloarthritis with radiographic sacroiliitis fulfil both the modified New York criteria and the ASAS axial spondyloarthritis criteria? Results from eight cohorts. Ann Rheum Dis 2019;78:1545–9.
    1. Baraliakos X. Imaging in axial spondyloarthritis. Isr Med Assoc J 2017;19:712–8.
    1. Østergaard M, Sorensen IJ. Magnetic resonance imaging—key to understanding and monitoring disease progression in spondyloarthritis? J Rheumatol 2015;42:1–4.
    1. Baraliakos X, Listing J, Rudwaleit M, Sieper J, Braun J. The relationship between inflammation and new bone formation in patients with ankylosing spondylitis. Arthritis Res Ther 2008;10:R104.
    1. van der Heijde D, Machado P, Braun J et al. MRI inflammation at the vertebral unit only marginally predicts new syndesmophyte formation: a multilevel analysis in patients with ankylosing spondylitis. Ann Rheum Dis 2012;71:369–73.
    1. Maksymowych WP, Chiowchanwisawakit P, Clare T et al. Inflammatory lesions of the spine on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis: evidence of a relationship between inflammation and new bone formation. Arthritis Rheum 2009;60:93–102.
    1. Kang KY, Kim IJ, Yoon MA et al. Fat metaplasia on sacroiliac joint magnetic resonance imaging at baseline is associated with spinal radiographic progression in patients with axial spondyloarthritis. PLoS One 2015;10:e0135206.
    1. Chiowchanwisawakit P, Lambert RG, Conner-Spady B, Maksymowych WP. Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis. Arthritis Rheum 2011;63:2215–25.
    1. Maksymowych WP, Wichuk S, Chiowchanwisawakit P, Lambert RG, Pedersen SJ. Fat metaplasia on MRI of the sacroiliac joints increases the propensity for disease progression in the spine of patients with spondyloarthritis. RMD Open 2017;3:e000399.
    1. Lambert RGW, Pedersen SJ, Maksymowych WP, Chiowchanwisawakit P, Østergaard M. Active inflammatory lesions detected by magnetic resonance imaging in the spine of patients with spondyloarthritis – definitions, assessment system, and reference image set. J Rheumatol 2009;84:3–17.
    1. Østergaard M, Maksymowych WP, Pedersen SJ, Chiowchanwisawakit P, Lambert RGW. Structural lesions detected by magnetic resonance imaging in the spine of patients with spondyloarthritis – definitions, assessment system, and reference image set. J Rheumatol 2009;84:18–34.
    1. Krabbe S, Sørensen IJ, Jensen B et al. Inflammatory and structural changes in vertebral bodies and posterior elements of the spine in axial spondyloarthritis: construct validity, responsiveness and discriminatory ability of the anatomy-based CANDEN scoring system in a randomised placebo-controlled trial. RMD Open 2018;4:e000624.
    1. Krabbe S, Østergaard M, Pedersen SJ et al. Canada-Denmark MRI scoring system of the spine in patients with axial spondyloarthritis: updated definitions, scoring rules and inter-reader reliability in a multiple reader setting. RMD Open 2019;5:e001057.
    1. Dougados M, Wei JC, Landewé R et al. Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W). Ann Rheum Dis 2020;79:176–85.
    1. European Medicines Agency. Upadacitinib summary of product characteristics. (29 March 2021, date last accessed).
    1. Schwartz DM, Bonelli M, Gadina M, O’Shea JJ. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol 2016;12:25–36.
    1. van der Heijde D, Baraliakos X, Gensler LS et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial. Lancet 2018;392:2378–87.
    1. Maksymowych WP, Inman RD, Salonen D et al. Spondyloarthritis Research Consortium of Canada magnetic resonance imaging index for assessment of spinal inflammation in ankylosing spondylitis. Arthritis Rheum 2005;53:502–9.
    1. Maksymowych WP, Inman RD, Salonen D et al. Spondyloarthritis Research Consortium of Canada magnetic resonance imaging index for assessment of sacroiliac joint inflammation in ankylosing spondylitis. Arthritis Rheum 2005;53:703–9.
    1. Braun J, Baraliakos X, Golder W et al. Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis, before and after successful therapy with infliximab: evaluation of a new scoring system. Arthritis Rheum 2003;48:1126–36.
    1. Haibel H, Rudwaleit M, Brandt HC et al. Adalimumab reduces spinal symptoms in active ankylosing spondylitis: clinical and magnetic resonance imaging results of a fifty-two-week open-label trial. Arthritis Rheum 2006;54:678–81.
    1. Baraliakos X, Boehm H, Bahrami R et al. What constitutes the fat signal detected by MRI in the spine of patients with ankylosing spondylitis? A prospective study based on biopsies obtained during planned spinal osteotomy to correct hyperkyphosis or spinal stenosis. Ann Rheum Dis 2019;78:1220–5.
    1. van der Heijde D, Dougados M, Landewé R et al. Sustained efficacy, safety and patient-reported outcomes of certolizumab pegol in axial spondyloarthritis: 4-year outcomes from RAPID-axSpA. Rheumatology (Oxford) 2017;56:1498–509.
    1. Maksymowych WP, Dougados M, van der Heijde D et al. Clinical and MRI responses to etanercept in early non-radiographic axial spondyloarthritis: 48-week results from the EMBARK study. Ann Rheum Dis 2016;75:1328–35.
    1. Weiß A, Song I-H, Haibel H, Listing J, Sieper J. Good correlation between changes in objective and subjective signs of inflammation in patients with short- but not long duration of axial spondyloarthritis treated with tumor necrosis factor-blockers. Arthritis Res Ther 2014;16:R35.
    1. Fu K, Robbins SR, McDougall JJ. Osteoarthritis: the genesis of pain. Rheumatology (Oxford) 2018;57:iv43–50.
    1. Mogard E, Olofsson T, Bergman S et al. Chronic pain and assessment of pain sensitivity in patients with axial spondyloarthritis: results from the SPARTAKUS cohort. J Rheumatol 2020;doi: 10.3899/jrheum.200872.
    1. Baraliakos X, Hermann KA, Xu S, Hsia EC, Braun J. Spinal mobility in the cervical and lumbar spine correlates with magnetic resonance imaging findings for inflammatory and structural changes in patients with active ankylosing spondylitis. Clin Exp Rheumatol 2020;38:467–71.
    1. Machado P, Landewé R, Braun J et al. Both structural damage and inflammation of the spine contribute to impairment of spinal mobility in patients with ankylosing spondylitis. Ann Rheum Dis 2010;69:1465–70.
    1. Carvalho PD, Ruyssen-Witrand A, Fonseca J, Marreiros A, Machado PM. Determining factors related to impaired spinal and hip mobility in patients with axial spondyloarthritis: longitudinal results from the DESIR cohort. RMD Open 2020;6:e001356.

Source: PubMed

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