ASDAS, BASDAI and different treatment responses and their relation to biomarkers of infl ammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNF alpha inhibitors

作者：Pedersen Susanne Juhl^*; Sorensen Inge Juul; Garnero Patrick; Johansen Julia Sidenius; Madsen Ole Rintek; Tvede Niels; Hansen Michael Sejer; Tham**org Gorm; Andersen Lis Smedegaard; Majgaard Ole; Loft Anne Gitte; Erlendsson Jon; Asmussen Karsten; Jurik Anne Grethe; Moller Jakob; Hasselquist Maria; Mikkelsen Dorrit; Skjodt Thomas; Lambert Robert; Hansen Annette; Ostergaard Mikkel

来源：Annals of the Rheumatic Diseases, 2011, 70(8): 1375-1381.

DOI：10.1136/ard.2010.138883

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 infl ammation (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 (TNF alpha) inhibitor therapy.
Methods ASDAS (CRP-based), BASDAI and biomarkers were determined before and seven times during 46 weeks of TNF alpha inhibitor therapy.
Results Very high ASDAS were associated with high levels of infl ammatory biomarkers, while high BASDAI were not related to any biomarkers. Mixed modeling demonstrated signifi cant 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 infl ammation, 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-TNF alpha 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 refl ect the infl ammatory disease processes. ClinicalTrials.gov identifi er NCT00133315.

• 出版日期2011-8