PMID- 25135077
OWN - NLM
STAT- MEDLINE
DCOM- 20150716
LR  - 20211021
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 16
IP  - 4
DP  - 2014 Aug 19
TI  - Calprotectin (S100A8/9) as serum biomarker for clinical response in 
      proof-of-concept trials in axial and peripheral spondyloarthritis.
PG  - 413
LID - 10.1186/s13075-014-0413-4 [doi]
LID - 413
AB  - INTRODUCTION: 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.
FAU - Turina, Maureen C
AU  - Turina MC
FAU - Yeremenko, Nataliya
AU  - Yeremenko N
FAU - Paramarta, Jacqueline E
AU  - Paramarta JE
FAU - De Rycke, Leen
AU  - De Rycke L
FAU - Baeten, Dominique
AU  - Baeten D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140819
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Biomarkers)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Leukocyte L1 Antigen Complex)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - B72HH48FLU (Infliximab)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Biomarkers/*blood
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Etanercept
MH  - Humans
MH  - Immunoglobulin G/therapeutic use
MH  - Infliximab
MH  - Leukocyte L1 Antigen Complex/*blood
MH  - Receptors, Tumor Necrosis Factor/therapeutic use
MH  - Sensitivity and Specificity
MH  - Spondylarthropathies/*blood/drug therapy
MH  - Spondylitis, Ankylosing/blood/drug therapy
PMC - PMC4293104
EDAT- 2014/08/20 06:00
MHDA- 2015/07/17 06:00
PMCR- 2014/08/19
CRDT- 2014/08/20 06:00
PHST- 2014/01/03 00:00 [received]
PHST- 2014/07/25 00:00 [accepted]
PHST- 2014/08/20 06:00 [entrez]
PHST- 2014/08/20 06:00 [pubmed]
PHST- 2015/07/17 06:00 [medline]
PHST- 2014/08/19 00:00 [pmc-release]
AID - s13075-014-0413-4 [pii]
AID - 413 [pii]
AID - 10.1186/s13075-014-0413-4 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2014 Aug 19;16(4):413. doi: 10.1186/s13075-014-0413-4.