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We aimed to identify and validate serum biomarkers with a high sensitivity to change upon effective treatment in spondyloarthritis (SpA) PoC trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The candidate biomarkers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), pentraxin-3 (PTX-3), alpha-2-macroglobulin (alpha-2-MG), matrix metalloproteinase-3 (MMP-3), calprotectin, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA) in healthy controls (\n                      <jats:italic>n<\/jats:italic>\n                      = 20) and SpA patients before and after 2 weeks of infliximab (\n                      <jats:italic>n<\/jats:italic>\n                      = 18) or placebo (\n                      <jats:italic>n<\/jats:italic>\n                      = 19) treatment in cohort 1. Clinical outcome was evaluated at week 12. Results were validated in ankylosing spondylitis (AS) with infliximab (cohort 2,\n                      <jats:italic>n<\/jats:italic>\n                      = 21) and peripheral SpA with etanercept (cohort 3,\n                      <jats:italic>n<\/jats:italic>\n                      = 20).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum levels of calprotectin, hs-CRP, PTX-3, VEGF (all\n                      <jats:italic>P<\/jats:italic>\n                      ?&lt;?0.001) and MMP-3 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.062), but not IL-6 and alpha-2-MG, were increased in SpA versus healthy controls. Treatment with infliximab, but not placebo, significantly decreased calprotectin (\n                      <jats:italic>P<\/jats:italic>\n                      ?&lt;?0.001) and hs-CRP (\n                      <jats:italic>P<\/jats:italic>\n                      ?&lt;?0.001) levels, with a similar trend for MMP-3 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.063). The standardized response mean (SRM), which reflects the ability to detect changes over time, was high for calprotectin (?1.26), good for hs-CRP (?0.96) and moderate for MMP-3 (?0.52). Calprotectin and hs-CRP, but not MMP-3, were good biomarkers for treatment response in axial and peripheral SpA as evaluated and confirmed in cohort 2 and 3 respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Calprotectin and hs-CRP are good serum biomarkers with high sensitivity to change upon effective treatment at the group level in small-scale, short term PoC trials in SpA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-014-0413-4","type":"journal-article","created":{"date-parts":[[2014,8,18]],"date-time":"2014-08-18T05:24:25Z","timestamp":1408339465000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Calprotectin (S100A8\/9) as serum biomarker for clinical response in proof-of-concept trials in axial and peripheral spondyloarthritis"],"prefix":"10.1186","volume":"16","author":[{"given":"Maureen C","family":"Turina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Yeremenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline E","family":"Paramarta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leen","family":"De Rycke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Baeten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,8,19]]},"reference":[{"key":"413_CR1","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1002\/art.511","volume":"46","author":"F Van den Bosch","year":"2002","unstructured":"Van den Bosch F, Kruithof E, Baeten D, Herssens A, de Keyser F, Mielants H, Veys EM: Randomized double-blind comparison of chimeric monoclonal antibody to tumor necrosis factor alpha (infliximab) versus placebo in active spondylarthropathy. 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