A prospective, randomized, placebo-controlled study to identify biomarkers associated with active treatment in psoriatic arthritis: Effects of adalimumab treatment on synovial tissue
Arno WR van Kuijk 1, Danielle M Gerlag 1, Koen Vos 2, Gertjan Wolbink 2, Marjan de Groot 1, Menno A de Rie 1, A H Zwinderman 1, Ben AC Dijkmans 3 and Paul P Tak 1*
1 Academic Medical Center / University of Amsterdam, Netherlands
2 Jan van Breemen Institute, Netherlands
3 VU University Medical Center, Netherlands
* To whom correspondence should be addressed. E-mail: p.p.tak{at}amc.uva.nl.
Accepted 13 July 2008
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Objective: To determine which of the changes in synovial tissue correlates best with clinical response associated with effective therapy (adalimumab) to facilitate the planning of future studies with therapeutic agents for psoriatic arthritis (PsA).
Methods: Twenty-four active PsA patients were randomized to receive adalimumab (n=12) or placebo (n=12) for 4 weeks. Synovial biopsies were obtained before and after 4 weeks of treatment. Immunohistochemical analysis was performed to characterize the cell infiltrate, expression of cytokines and matrix metalloproteinases (MMPs), and vascularity. Sections were analyzed by digital image analysis. Statistical analysis was performed using covariance analysis.
Results The mean DAS28 after 4 weeks was 1.92 units lower (95% confidence interval (CI) 1.07 - 2.77) after adalimumab therapy compared with placebo. Paired pre- and post-treatment synovial samples were available from 19 patients. Many cell types were reduced after adalimumab treatment compared to placebo. After applying a ranked ANCOVA model to correct for baseline imbalances, a significant effect of treatment was observed on CD3 positive cells: there was a median reduction of 248 cells/mm2 after adalimumab versus placebo treatment (P = 0.035). In addition, the expression of MMP-13 was significantly reduced after active treatment: the integrated optical density (IOD)/mm2 was 18,190 lower after adalimumab treatment as compared to placebo (P = 0.033).
Conclusion: Adalimumab therapy in PsA is associated with a marked reduction in T cell infiltration and MMP-13 expression in synovial tissue, suggesting that these parameters could be used as biomarkers that are sensitive to change after active treatment in small proof of concept studies in PsA.
