与TNF拮抗剂治疗AS临床和MRI疗效相关的血清生物标记物

与TNF拮抗剂治疗AS临床和MRI疗效相关的血清生物标记物

PresentID:
THU0223

SERUM BIOMARKERS ASSOCIATED WITH CHANGES IN ASDAS AND MRI FOLLOWING TREATMENT OF ANKYLOSING SPONDYLITIS WITH GOLIMUMAB R. D. Inman1,*, X. Baraliakos2, K.-G. Hermann3, J. Braun2, A. Deodhar4, D. F. van der Heijde5, S. Xu6, B. Hsu6 1University of Toronto, Toronto, Canada, 2Rheumazentrum Ruhrgebiet, Herne, 3Charité Hospital, Berlin, Germany, 4Oregon Health Science University, Portland, United States, 5Leiden University Medical Center, Leiden, Netherlands, 6Janssen R&D, LLC., Spring House, United States Background: Serum biomarkers that can predict subsequent clinical or imaging outcomes would aid decision-making in the management of ankylosing spondylitis (AS). Objectives: Using data from the golimumab (GLM) study, GO-RAISE, in patients with active AS, we analysed correlations between multiple serum biomarkers and inflammation as detected by magnetic resonance imaging (MRI) and AS Disease Activity Score (ASDAS). Methods: In GO-RAISE, patients with moderately to severely active AS were randomized to SC GLM 50mg, 100mg, or PBO q4wks. PBO-treated patients crossed over to receive GLM at wk16 or 24. Spinal MRIs in the sagittal plane were acquired using 1.5T scanners with T1 and short tau inversion recovery (STIR) sequences at BL and wk14. 98 patients were scored for activity (ASspiMRIa) and structural (ASspiMRI-c) scores. Radiographs and MRIs were assessed by 2 readers who were blinded to treatment and image time order. Mean scores were used for analyses. Sera were collected from 140 patients at baseline and wk14 for analysis of markers by ELISA and/or using a multiplex platform (Rules Based Medicine).  Spearman correlation analyses with Bonferoni p-value adjustment and logistic regression were conducted to assess the relationship between 76 serum biomarker levels and ASDAS using C-reactive protein (ASDAS), ASspiMRI-a, or MRI-c score at various time points. Results: Baseline ASDAS showed significant correlations with serum biomarkers for inflammation (IL-6, ICAM-1, haptoglobin, amyloid P) and lipid metabolism (Complement C3). BL IL-6 or TIMP-1 correlated with the reduction of ASspiMRI-a at wk14 in GLM-treated patients. Wk4 change in IL-6 and C3 also showed correlation with change in ASspiMRI-a at wk14. Development of new fatty degeneration in the spine at wk14 correlated with BL biomarkers involved in lipid metabolism (leptin, C3) and tissue remodeling (TIMP-1). Previously described predictors such as insulin, MMP-3, VEGF, or bone resorption markers did not have significant correlations with clinical or imaging outcomes. Conclusions: This analysis suggests that serum biomarkers IL-6, TIMP-1, and C3 may be linked to a reduction in spinal inflammation in AS patients following GLM treatment.  In addition, ICAM-1, haptoglobin and amyloid P correlate with baseline disease activity and may implicate novel roles for these factors in AS-related inflammation.

背景：能够预测临床或影像学结局的血清生物标记有助于AS患者的治疗决策。 目的：数据来源于TNF拮抗剂治疗活动性强直性脊柱炎(AS)患者的研究，分析了多项血清生物标记物与炎症（MRI）、ASDAS的相关性。 方法：该研究中，中重度AS患者随机接受某TNF拮抗剂 50mg、 100mg或安慰剂治疗。16或24周时，安慰剂组患者开始接受TNF拮抗剂治疗。基线和14周评估脊柱MRI（T1和STIR）。98例患者评估脊柱炎症（ASspiMRI-a）和结构（ASspiMRI-c）。2位阅片师盲态评估放射学和MRI资料。所有数据以平均值纳入分析。收集140例患者基线和14周的血清，用ELISA法和/或多通道检测平台(Rules Based Medicine)分析标记物。采用Bonferoni P值校正的Spearman相关分析和逻辑回归评价76种血清标记物与ASDAS-CRP、ASspiMRI-a、ASspiMRI-c在各个时间点的相关性。 结果：基线ASDAS分别与炎性血清标记物（IL-6、ICAM-1、结合珠蛋白、淀粉样P物质）和脂类代谢物（补体C3）有显著相关性。TNF拮抗剂治疗患者中，基线IL-6或TIMP-1与14周ASspiMRI-a下降相关。4周时IL-6和C3改变情况与14周ASspiMRI-a改变相关。基线脂类代谢标记物（Leptin、C3）和组织重塑标记物（TIMP-1）与14周脊柱新发脂肪沉积相关联。既往报道的预测因素，诸如胰岛素、MMP-3、VEGF或骨吸收标记物与临床/影像结果无显著相关性。 结论：本研究分析结果显示，血清生物标记物IL-6、TIMP-1和C3可能与AS患者接受TNF拮抗剂治疗后脊柱炎症消退有关。此外，血清ICAM-1、结合珠蛋白和淀粉样P物质与基线疾病活动度相关，并提示这些因素在AS相关炎症中的新作用。