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THU0223 Serum Biomarkers Associated with Changes in Asdas and MRI Following Treatment of Ankylosing Spondylitis with Golimumab
  1. R.D. Inman1,
  2. X. Baraliakos2,
  3. K.-G. Hermann3,
  4. J. Braun2,
  5. A. Deodhar4,
  6. D.F. van der Heijde5,
  7. S. Xu6,
  8. B. Hsu6
  1. 1University of Toronto, Toronto, Canada
  2. 2Rheumazentrum Ruhrgebiet, Herne
  3. 3Charité Hospital, Berlin, Germany
  4. 4Oregon Health Science University, Portland, United States
  5. 5Leiden University Medical Center, Leiden, Netherlands
  6. 6Janssen R&D, LLC., Spring House, United States

Abstract

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 (ASspiMRI-a) 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.

Disclosure of Interest R. Inman Grant/research support from: Janssen R&D, LLC., X. Baraliakos Grant/research support from: Janssen R&D, LLC., K.-G. Hermann Grant/research support from: Janssen R&D, LLC., J. Braun Grant/research support from: Janssen R&D, LLC., A. Deodhar Grant/research support from: Janssen R&D, LLC., D. van der Heijde Grant/research support from: Janssen R&D, LLC., S. Xu Employee of: Janssen R&D, LLC., B. Hsu Employee of: Janssen R&D, LLC.

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