Soluble biomarkers of cartilage and bone metabolism in early proof of concept trials in psoriatic arthritis: effects of adalimumab versus placebo.
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.
van Kuijk
Arno W R
AW
Division of Clinical Immunology and Rheumatology, F4-218, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
DeGroot
Jeroen
J
Koeman
Rishma C
RC
Sakkee
Nico
N
Baeten
Dominique L
DL
Gerlag
Danielle M
DM
Tak
Paul P
PP
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D010919:Placebos; D000068879:Adalimumab