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

Susanne Juhl Pedersen, Inge Juul Sørensen, Patrick Garnero, Julia Sidenius Johansen, Ole Rintek Madsen, Niels Tvede, Michael Sejer Hansen, Gorm Thamsborg, Lis Smedegaard Andersen, Ole Majgaard, Anne Gitte Loft, Jon Erlendsson, Karsten Asmussen, Anne Grethe Jurik, Jakob Møller, Maria Hasselquist, Dorrit Mikkelsen, Thomas Skjødt, Robert Lambert, Annette Hansen, Mikkel Østergaard
Annals of the Rheumatic Diseases 2011, 70 (8): 1375-81

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. identifier NCT00133315.

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