title: Calprotectin (S100A8/9) as serum biomarker for clinical response in proof-of-concept trials in axial and peripheral spondyloarthritis.
abstract: BACKGROUND
  Biomarkers complementing clinical evaluations may help to reduce the length and size of proof-of-concept (PoC) trials aimed to obtain quick "go/no go" decisions in the clinical development of new treatments. We aimed to identify and validate serum biomarkers with a high sensitivity to change upon effective treatment in spondyloarthritis (SpA) PoC trials.
  
  
  METHODS
  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 = 20) and SpA patients before and after 2 weeks of infliximab (n = 18) or placebo (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 = 21) and peripheral SpA with etanercept (cohort 3, n = 20).
  
  
  RESULTS
  Serum levels of calprotectin, hs-CRP, PTX-3, VEGF (all P < 0.001) and MMP-3 (P = 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 (P < 0.001) and hs-CRP (P < 0.001) levels, with a similar trend for MMP-3 (P = 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Maureen C
authors.initials: MC
authors.lastname: Turina
authors.forename: Nataliya
authors.initials: N
authors.lastname: Yeremenko
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Paramarta
authors.forename: Leen
authors.initials: L
authors.lastname: De Rycke
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D039841:Leukocyte L1 Antigen Complex / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D025242:Spondylarthropathies / Q000097:blood* / Q000188:drug therapy; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000188:drug therapy
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007074:Immunoglobulin G; D039841:Leukocyte L1 Antigen Complex; D018124:Receptors, Tumor Necrosis Factor; D000069285:Infliximab; D000068800:Etanercept