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ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors
  1. Susanne Juhl Pedersen1,2,
  2. Inge Juul Sørensen3,4,5,
  3. Patrick Garnero6,7,
  4. Julia Sidenius Johansen18,
  5. Ole Rintek Madsen2,
  6. Niels Tvede8,
  7. Michael Sejer Hansen2,
  8. Gorm Thamsborg4,
  9. Lis Smedegaard Andersen9,
  10. Ole Majgaard3,
  11. Anne Gitte Loft10,
  12. Jon Erlendsson11,
  13. Karsten Asmussen12,
  14. Anne Grethe Jurik13,
  15. Jakob Møller14,
  16. Maria Hasselquist14,
  17. Dorrit Mikkelsen15,
  18. Thomas Skjødt16,
  19. Robert Lambert17,
  20. Annette Hansen7,
  21. Mikkel Østergaard3,5
  1. 1Rheumatologic Research Unit, Glostrup University Hospital, Copenhagen, Denmark
  2. 2Department of Rheumatology, Gentofte University Hospital, Copenhagen, Denmark
  3. 3Department of Rheumatology, Hvidovre University Hospital, Copenhagen, Denmark
  4. 4Department of Rheumatology, Glostrup University Hospital, Copenhagen, Denmark
  5. 5The DANBIO Database, Department of Rheumatology, Hvidovre University Hospitals, Copenhagen, Denmark
  6. 6INSERM Unit 664, Lyon, France
  7. 7Cisbio Bioassays, Bagnols/Cèze, France
  8. 8Department of Rheumatology, Rigshopitalet, Copenhagen, Denmark
  9. 9Rheumatism Hospital, University of Southern Denmark, Gråsten, Denmark
  10. 10Department of Rheumatology, Vejle Hospital, Vejle, Denmark
  11. 11Department of Rheumatology, Horsens Hospital, Horsens, Denmark
  12. 12Department of Rheumatology, Bispebjerg University Hospital, Copenhagen, Denmark
  13. 13Departments of Radiology, Aarhus University Hospital, Aarhus, Denmark
  14. 14Department of Radiology, Herlev University Hospital, Copenhagen, Denmark
  15. 15Thava Aabenraa, Sygehus Sønderjylland, Aabenraa, Denmark
  16. 16Department of Radiology, Vejle Hospital, Vejle, Denmark
  17. 17Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Canada
  18. 18Department of Oncology and Medicine, Herlev University Hospital, Copenhagen, Denmark
  1. Correspondence to Susanne Juhl Pedersen, Department of Rheumatology, C Post 535, Gentofte University Hospital, Niels Andersens Vej 65, DK-2900 Hellerup, Denmark; susanne_juhl_ped{at}dadlnet.dk

Abstract

Objectives To investigate the relation between ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) and treatment response and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40), angiogenesis (vascular endothelial growth factor (VEGF)), cartilage (C-terminal crosslinking telopeptide of type II collagen (CTX-II), matrix metalloproteinase-3 (MMP-3), total aggrecan, cartilage oligomeric matrix protein) and bone (C-terminal crosslinking telopeptide of type I collagen, osteocalcin) turnover in 60 patients with axial spondyloarthritis initiating tumour necrosis factor alpha (TNFα) inhibitor therapy.

Methods ASDAS (CRP-based), BASDAI and biomarkers were determined before and seven times during 46 weeks of TNFα inhibitor therapy.

Results Very high ASDAS were associated with high levels of inflammatory biomarkers, while high BASDAI were not related to any biomarkers. Mixed modeling demonstrated significant longitudinal associations between ASDAS and IL-6, VEGF, MMP-3 and osteocalcin and between BASDAI and CRP, IL-6 and VEGF. Major improvement in ASDAS was associated with larger percentage decreases in biomarkers of inflammation, angiogenesis, MMP-3 and increases in aggrecan and osteocalcin. BASDAI response was associated with larger decreases in CRP and IL-6. Biomarkers with moderate/high differences in responsiveness for major versus no/clinically important improvement in ASDAS were CRP, IL-6, VEGF, aggrecan and osteocalcin, and VEGF and CTX-II for BASDAI response versus non-response.

Conclusion Levels and changes of 10 biomarkers in patients with axial spondyloarthritis during anti-TNFα therapy were documented. Construct validity and responsiveness of IL-6, VEGF, MMP-3, total aggrecan and osteocalcin were demonstrated. ASDAS was more associated with these biomarkers than BASDAI, and may better reflect the inflammatory disease processes.

ClinicalTrials.gov identifier NCT00133315.

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Footnotes

  • Funding SJP's salary during her position as a PhD student was financed by the Faculty of Health Sciences, University of Copenhagen, Denmark. Furthermore, the authors are grateful for the grant support received for the biomarker analyses: the Danish Rheumatism Association; the Danish Psoriasis Research Foundation; the Toyota Foundation in Denmark; the Research Council of Herlev Hospital; the Bjarne Jensen Foundation; the A.P. Møller Foundation for the Advancement of Medical Science; the Foundation of 1870; the Scandinavian Journal of Rheumatology's grant; Oldermand Slagtermester Peter Ryholts Grant. The University of Copenhagen and the above-mentioned associations and foundations all provided non-profit funding and played no role in the design and conduct of the study; or in the collection, analysis, and interpretation of the data; or in the preparation, review and approval of the manuscript.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the local ethics commitee in Copenhagen.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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