TY - JOUR
T1 - Serum biomarkers and changes in clinical/MRI evidence of golimumab-treated patients with ankylosing spondylitis
T2 - Results of the randomized, placebo-controlled GO-RAISE study
AU - Inman, Robert D.
AU - Baraliakos, Xenofon
AU - Hermann, Kay Geert A.
AU - Braun, Jürgen
AU - Deodhar, Atul
AU - van der Heijde, Désirée
AU - Xu, Stephen
AU - Hsu, Benjamin
N1 - Publisher Copyright:
© 2016 The Author(s).
PY - 2016/12/28
Y1 - 2016/12/28
N2 - Background: In the present study, we evaluated relationships between serum biomarkers and clinical/magnetic resonance imaging (MRI) findings in golimumab-treated patients with ankylosing spondylitis. Methods: In the GO-RAISE study, 356 patients with ankylosing spondylitis randomly received either placebo (n = 78) or golimumab 50mg or 100mg (n = 278) injections every 4weeks 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 s) 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. Results: 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 s = 0.39-0.66, p ≤ 0.01). Only baseline leptin significantly correlated with ASDAS improvement at week 104 (r s = 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 2 = 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 s = 0.55, p = 0.001) and week 14 (r s = 0.49, p = 0.040) significantly correlated with BASDAI improvement at week 14. Baseline IL-6 and TIMP-1 (r s = 0.63, 0.67; p < 0.05) and reductions at week 4 in IL-6 (r s = 0.61, p < 0.05) and C3 (r s = 0.72; p < 0.05) significantly correlated with week 14 ASspiMRI-a improvement. Conclusions: 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. Trial registration: ClinicalTrials.gov identifier: NCT00265083. Registered on 12 December 2005.
AB - Background: In the present study, we evaluated relationships between serum biomarkers and clinical/magnetic resonance imaging (MRI) findings in golimumab-treated patients with ankylosing spondylitis. Methods: In the GO-RAISE study, 356 patients with ankylosing spondylitis randomly received either placebo (n = 78) or golimumab 50mg or 100mg (n = 278) injections every 4weeks 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 s) 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. Results: 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 s = 0.39-0.66, p ≤ 0.01). Only baseline leptin significantly correlated with ASDAS improvement at week 104 (r s = 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 2 = 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 s = 0.55, p = 0.001) and week 14 (r s = 0.49, p = 0.040) significantly correlated with BASDAI improvement at week 14. Baseline IL-6 and TIMP-1 (r s = 0.63, 0.67; p < 0.05) and reductions at week 4 in IL-6 (r s = 0.61, p < 0.05) and C3 (r s = 0.72; p < 0.05) significantly correlated with week 14 ASspiMRI-a improvement. Conclusions: 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. Trial registration: ClinicalTrials.gov identifier: NCT00265083. Registered on 12 December 2005.
KW - ASDAS
KW - Biologic
KW - MRI
KW - Monoclonal antibody
KW - TNF inhibitor
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U2 - 10.1186/s13075-016-1200-1
DO - 10.1186/s13075-016-1200-1
M3 - Article
C2 - 28031053
AN - SCOPUS:85007422349
SN - 1478-6354
VL - 18
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - 304
ER -