Soluble Biomarkers of Cartilage and Bone Metabolism in Early Proof of Concept
Trials in Psoriatic Arthritis: Effects of Adalimumab Versus Placebo |
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| Authors: | Arno W R van Kuijk Jeroen DeGroot Rishma C Koeman Nico Sakkee Dominique L Baeten Danielle M Gerlag Paul P Tak |
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| Institution: | 1. Division of Clinical Immunology and Rheumatology, F4-218, Academic Medical
Center/University of Amsterdam, Amsterdam, The Netherlands.; 2. Business Unit Biosciences, The Netherlands Organization for Applied Scientific
Research (TNO) Quality of Life, Leiden, The Netherlands.;Hôpital Cochin, France |
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| Abstract: | BackgroundThere 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.Materials and MethodsTwenty-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).ResultsAfter 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.ConclusionMMP-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.Trial RegistrationCurrent Controlled Trials ISRCTN23328456 |
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