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 levelfor screening purposes in small proof of principle studies during early drugdevelopment. We investigated early changes in serum levels of several candidatebiomarkers involved in cartilage and bone metabolism following the initiation ofadalimumab as a prototypic active treatment in psoriatic arthritis (PsA) compared toplacebo.

Materials and Methods

Twenty-four PsA patients were randomized to receive either adalimumab 40 mg s.c. everyother week or placebo for 4 weeks, followed by an open label extension phase. Serumsamples were obtained at baseline and after 4 and 12 weeks of treatment and analyzed forlevels of CPII and PINP (synthesis of type II and type I procollagen), melanomainhibitory activity (MIA) (chondrocyte anabolism), matrix metalloproteinase (MMP)-3, C2Cand cartilage oligomeric matrix protein (COMP) (type II collagen degradation),osteocalcin (OC) (bone formation), NTX-I and ICTP (both type I collagendegradation).

Results

After 4 weeks, there was a significant decrease in serum MMP-3 levels inadalimumab-treated patients (P<0.005), while no change was observed in theplacebo 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 markedreduction in serum MMP-3 in both groups (P<0.005), whereas other markers did notshow significant changes compared to baseline.

Conclusion

MMP-3 and MIA could serve as soluble biomarkers associated with inflammation as well asjoint remodelling and destruction and may, together with clinical evaluation and incombination with other biomarkers, assist in distinguishing between effective andineffective therapy in small, proof-of-principle studies of short duration in PsA.

Trial Registration

Current Controlled Trials ISRCTN23328456