title: Soluble biomarkers of cartilage and bone metabolism in early proof of concept trials in psoriatic arthritis: effects of adalimumab versus placebo.
abstract: BACKGROUND
  There is growing interest in soluble biomarkers that could be used on the group level for screening purposes in small proof of principle studies during early drug development. We investigated early changes in serum levels of several candidate biomarkers involved in cartilage and bone metabolism following the initiation of adalimumab as a prototypic active treatment in psoriatic arthritis (PsA) compared to placebo.
  
  
  METHODS
  Twenty-four PsA patients were randomized to receive either adalimumab 40 mg s.c. every other week or placebo for 4 weeks, followed by an open label extension phase. Serum samples were obtained at baseline and after 4 and 12 weeks of treatment and analyzed for levels of CPII and PINP (synthesis of type II and type I procollagen), melanoma inhibitory activity (MIA) (chondrocyte anabolism), matrix metalloproteinase (MMP)-3, C2C and cartilage oligomeric matrix protein (COMP) (type II collagen degradation), osteocalcin (OC) (bone formation), NTX-I and ICTP (both type I collagen degradation).
  
  
  RESULTS
  After 4 weeks, there was a significant decrease in serum MMP-3 levels in adalimumab-treated patients (P<0.005), while no change was observed in the placebo group. A significant increase in serum MIA was noted after adalimumab therapy (P<0.005) but not after placebo treatment. After 12 weeks, there was a marked reduction in serum MMP-3 in both groups (P<0.005), whereas other markers did not show significant changes compared to baseline.
  
  
  CONCLUSIONS
  MMP-3 and MIA could serve as soluble biomarkers associated with inflammation as well as joint remodelling and destruction and may, together with clinical evaluation and in combination with other biomarkers, assist in distinguishing between effective and ineffective therapy in small, proof-of-principle studies of short duration in PsA.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN23328456.
authors.affiliation: Division of Clinical Immunology and Rheumatology, F4-218, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Arno W R
authors.initials: AW
authors.lastname: van Kuijk
authors.forename: Jeroen
authors.initials: J
authors.lastname: DeGroot
authors.forename: Rishma C
authors.initials: RC
authors.lastname: Koeman
authors.forename: Nico
authors.initials: N
authors.lastname: Sakkee
authors.forename: Dominique L
authors.initials: DL
authors.lastname: Baeten
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Gerlag
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D061067:Antibodies, Monoclonal, Humanized; D015535:Arthritis, Psoriatic / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood*; D001842:Bone and Bones / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D010919:Placebos; D000068879:Adalimumab