生物标志物与临床参数相比在预测轴性脊柱关节炎放射学进展方面的附加价值。

Added value of biomarkers compared with clinical parameters for the prediction of radiographic spinal progression in axial spondyloarthritis.

机构信息

Department of Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin.

Berlin Institute of Health, Berlin.

出版信息

Rheumatology (Oxford). 2019 Sep 1;58(9):1556-1564. doi: 10.1093/rheumatology/kez025.

DOI:10.1093/rheumatology/kez025

PMID:30830164

Abstract

OBJECTIVES

The objective of this study was to examine whether adding biomarkers to routine clinical parameters improves prediction of radiographic spinal progression in axial spondyloarthritis.

METHODS

One hundred and seventeen patients with ankylosing spondylitis who completed the Effects of NSAIDs on RAdiographic Damage in Ankylosing Spondylitis (ENRADAS) trial were included. Radiographic spinal progression was defined as worsening of the modified Stoke Ankylosing Spondylitis Spine Score by ⩾2 points after 2 years. A clinical prediction model was constructed out of baseline syndesmophytes, elevated CRP, cigarette smoking and male sex. The following serum biomarkers were measured at baseline by ELISA: MMP3, VEGF, calprotectin, leptin, high molecular weight adiponectin, osteoprotegerin, sclerostin, N-terminal telopeptide, procollagen type II N-terminal propeptide and serum amyloid A.

RESULTS

Repeated cross-validation analyses revealed one biomarker combination with potential added predictive value in addition to the clinical model: leptin + high molecular weight adiponectin + VEGF. This biomarker combination showed an area under the curve (AUC)Biomarkers = 0.731 (95% CI: 0.614, 0.848), which was numerically superior to the clinical model [AUCClinical = 0.665 (95% CI: 0.553, 0.776)]. A combination of clinical parameters + biomarkers showed an improved predictive value compared with the clinical model reflected by AUCClinical+Biomarkers = 0.768 (95% CI: 0.666, 0.871), though not statistically significant (P = 0.051). However, by considering the part of the receiver operating characteristic curve with a specificity ⩾75% resulting in partial AUC (pAUC), the improvement becomes significant (pAUCClinical+Biomarkers = 0.119; pAUCClinical = 0.053; P = 0.01).

CONCLUSION

Biomarkers show potential to improve the prediction of radiographic spinal progression in axial spondyloarthritis when used in addition to the clinical parameters, though the added value seems to be rather small.

摘要

目的

本研究旨在探讨在常规临床参数的基础上加入生物标志物是否能提高对强直性脊柱炎影像学脊柱进展的预测。

方法

共纳入 117 例完成 NSAIDs 对强直性脊柱炎放射学损害的影响（ENRADAS）试验的强直性脊柱炎患者。影像学脊柱进展定义为 2 年后改良 Stoke 强直性脊柱炎脊柱评分 ⩾2 分的恶化。采用基线附着点骨赘、C 反应蛋白升高、吸烟和男性等临床预测模型。通过 ELISA 法在基线时测量以下血清生物标志物：基质金属蛋白酶 3（MMP3）、血管内皮生长因子（VEGF）、钙卫蛋白、瘦素、高分子量脂联素、骨保护素、骨硬化蛋白、N 端肽、Ⅱ型前胶原氨基端前肽和血清淀粉样蛋白 A。

结果

重复交叉验证分析显示，除临床模型外，还有一种生物标志物组合具有潜在的附加预测价值：瘦素+高分子量脂联素+VEGF。该生物标志物组合的曲线下面积（AUC）Biomarkers = 0.731（95%CI：0.614，0.848），数值优于临床模型[AUCClinical = 0.665（95%CI：0.553，0.776）]。与临床模型相比，临床参数+生物标志物的组合具有更好的预测价值，反映在 AUCClinical+Biomarkers = 0.768（95%CI：0.666，0.871），但无统计学意义（P = 0.051）。然而，考虑到特异性 ⩾75%的接收器操作特征曲线的一部分，即部分 AUC（pAUC），则改善具有统计学意义（pAUCClinical+Biomarkers = 0.119；pAUCClinical = 0.053；P = 0.01）。