Inman Robert D, Baraliakos Xenofon, Hermann Kay-Geert A, Braun Jürgen, Deodhar Atul, van der Heijde Désirée, Xu Stephen, Hsu Benjamin
Department of Immunology, University of Toronto, Toronto, ON, Canada.
Department of Medicine, University of Toronto, Toronto, ON, Canada.
Arthritis Res Ther. 2016 Dec 28;18(1):304. doi: 10.1186/s13075-016-1200-1.
In the present study, we evaluated relationships between serum biomarkers and clinical/magnetic resonance imaging (MRI) findings in golimumab-treated patients with ankylosing spondylitis.
In the GO-RAISE study, 356 patients with ankylosing spondylitis randomly received either placebo (n = 78) or golimumab 50 mg or 100 mg (n = 278) injections every 4 weeks through week 24 (placebo-controlled); patients continuing GO-RAISE received golimumab through week 252. Up to 139/125 patients had sera collected for biomarkers/serial spine MRI scans (sagittal plane, 1.5-T scanner). Two blinded readers employed modified ankylosing spondylitis spine magnetic resonance imaging score for activity (ASspiMRI-a) and ankylosing spondylitis spine magnetic resonance imaging score for chronicity. Spearman correlations (r ) were assessed between serum biomarkers (n = 73) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), C-reactive-protein (CRP)-based Ankylosing Spondylitis Disease Activity Score (ASDAS), modified Stokes Ankylosing Spondylitis Spine Score (mSASSS), and ASspiMRI scores. Serum biomarkers predicting postbaseline spinal fatty lesion development and inflammation were analyzed by logistic regression.
Significant, moderately strong correlations were observed between baseline inflammatory markers interleukin (IL)-6, intracellular adhesion molecule-1, complement component 3 (C3), CRP, haptoglobin, and serum amyloid-P and baseline ASDAS (r = 0.39-0.66, p ≤ 0.01). Only baseline leptin significantly correlated with ASDAS improvement at week 104 (r = 0.55, p = 0.040), and only baseline IL-6 significantly predicted mSASSS week 104 change (β = 0.236, SE = 0.073, p = 0.002, model R = 0.093). By logistic regression, baseline leptin, C3, and tissue inhibitor of metalloproteinase (TIMP)-1 correlated with new fatty lesions per spinal MRI at week 14 and week 104 (both p < 0.01). Changes in serum C3 levels at week 4 (r = 0.55, p = 0.001) and week 14 (r = 0.49, p = 0.040) significantly correlated with BASDAI improvement at week 14. Baseline IL-6 and TIMP-1 (r = -0.63, -0.67; p < 0.05) and reductions at week 4 in IL-6 (r = 0.61, p < 0.05) and C3 (r = 0.72; p < 0.05) significantly correlated with week 14 ASspiMRI-a improvement.
Extensive serum biomarker multiparametric analyses in golimumab-treated patients with ankylosing spondylitis demonstrated few correlations with disease activity or MRI changes; IL-6 weakly correlated with radiographic progression.
ClinicalTrials.gov identifier: NCT00265083 . Registered on 12 December 2005.
在本研究中，我们评估了接受戈利木单抗治疗的强直性脊柱炎患者血清生物标志物与临床/磁共振成像（MRI）结果之间的关系。
在GO-RAISE研究中，356例强直性脊柱炎患者被随机分配，每4周接受一次安慰剂（n = 78）或50 mg或100 mg戈利木单抗注射（n = 278），共治疗24周（安慰剂对照）；继续参与GO-RAISE研究的患者接受戈利木单抗治疗至252周。多达139/125例患者采集血清用于生物标志物检测/脊柱MRI序列扫描（矢状面，1.5-T扫描仪）。两名盲法阅片者采用改良的强直性脊柱炎脊柱磁共振成像活动度评分（ASspiMRI-a）和强直性脊柱炎脊柱磁共振成像慢性度评分。评估血清生物标志物（n = 73）与巴斯强直性脊柱炎疾病活动指数（BASDAI）、基于C反应蛋白（CRP）的强直性脊柱炎疾病活动评分（ASDAS）、改良斯托克斯强直性脊柱炎脊柱评分（mSASSS）以及ASspiMRI评分之间的Spearman相关性（r）。通过逻辑回归分析预测基线后脊柱脂肪病变发展和炎症的血清生物标志物。
观察到基线炎症标志物白细胞介素（IL）-6、细胞间黏附分子-1、补体成分3（C3）、CRP、触珠蛋白和血清淀粉样蛋白-P与基线ASDAS之间存在显著的中度强相关性（r = 0.39 - 0.66，p≤0.01）。仅基线瘦素与第104周时ASDAS的改善显著相关（r = 0.55，p = 0.040），且仅基线IL-6显著预测第104周时mSASSS的变化（β = 0.236，SE = 0.073，p = 0.002，模型R = 0.093）。通过逻辑回归分析，基线瘦素、C3和基质金属蛋白酶组织抑制剂（TIMP）-1与第14周和第104周时每例脊柱MRI出现的新脂肪病变相关（均p < 0.01）。第4周（r = 0.55，p = 0.001）和第14周（r = 0.49，p = 0.040）时血清C3水平的变化与第14周时BASDAI的改善显著相关。基线IL-6和TIMP-1（r = -0.63，-0.67；p < 0.05）以及第4周时IL-6（r = 0.61，p < 0.05）和C3（r = 0.72；p < 0.05）的降低与第14周时ASspiMRI-a的改善显著相关。
在接受戈利木单抗治疗的强直性脊柱炎患者中进行的广泛血清生物标志物多参数分析显示，与疾病活动或MRI变化的相关性较少；IL-6与影像学进展的相关性较弱。
ClinicalTrials.gov标识符：NCT00265083。于2005年12月12日注册。
