Rheumatologic Research Unit, Glostrup University Hospital, Copenhagen, Denmark.
Ann Rheum Dis. 2011 Aug;70(8):1375-81. doi: 10.1136/ard.2010.138883. Epub 2011 May 8.
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.
ASDAS (CRP-based), BASDAI and biomarkers were determined before and seven times during 46 weeks of TNFα inhibitor therapy.
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.
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.
研究强直性脊柱炎疾病活动评分（ASDAS）、Bath 强直性脊柱炎疾病活动指数（BASDAI）与炎症标志物（C 反应蛋白（CRP）、白细胞介素 6（IL-6）、YKL-40）、血管生成（血管内皮生长因子（VEGF））、软骨（Ⅱ型胶原 C 端交联肽（CTX-II）、基质金属蛋白酶 3（MMP-3）、总聚集蛋白、软骨寡聚基质蛋白）和骨（Ⅰ型胶原 C 端交联肽、骨钙素）转换之间的关系在 60 例开始肿瘤坏死因子 α（TNFα）抑制剂治疗的轴性脊柱关节炎患者中的作用。
在 TNFα 抑制剂治疗的 46 周内，分别在治疗前和第 7 次测定 ASDAS（基于 CRP）、BASDAI 和生物标志物。
非常高的 ASDAS 与高水平的炎症生物标志物相关，而高 BASDAI 与任何生物标志物均无关。混合模型显示 ASDAS 与 IL-6、VEGF、MMP-3 和骨钙素之间以及 BASDAI 与 CRP、IL-6 和 VEGF 之间存在显著的纵向关联。ASDAS 的显著改善与炎症、血管生成、MMP-3 标志物的百分比降低以及聚集蛋白和骨钙素的增加有关。BASDAI 的反应与 CRP 和 IL-6 的减少有关。在 ASDAS 主要改善与无/临床重要改善相比，生物标志物的反应性有中度/高度差异，而在 BASDAI 反应与无反应相比，生物标志物的反应性有中度/高度差异的生物标志物是 CRP、IL-6、VEGF、聚集蛋白和骨钙素，以及 VEGF 和 CTX-II。
在接受抗 TNFα 治疗的轴性脊柱关节炎患者中，记录了 10 种生物标志物的水平和变化。证明了白细胞介素 6、VEGF、MMP-3、总聚集蛋白和骨钙素的结构有效性和反应性。ASDAS 与这些生物标志物的相关性优于 BASDAI，可能更好地反映炎症性疾病过程。临床试验.gov 标识符 NCT00133315。
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