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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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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