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Journal of Immunology Research
Volume 2015, Article ID 906349, 10 pages
http://dx.doi.org/10.1155/2015/906349
Clinical Study

The Pharmacodynamic Impact of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, on Circulating Levels of Inflammatory Biomarkers in Patients with Psoriatic Arthritis: Substudy Results from a Phase III, Randomized, Placebo-Controlled Trial (PALACE 1)

1Translational Development, Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA
2Biostatistics, Celgene Corporation, 33 Technology Drive, Warren, NJ 07059, USA

Received 26 September 2014; Accepted 10 January 2015

Academic Editor: Marco Antonio Velasco-Velázquez

Copyright © 2015 Peter H. Schafer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated effectiveness (versus placebo) for treatment of active psoriatic arthritis in the psoriatic arthritis long-term assessment of clinical efficacy (PALACE) phase III clinical trial program. Pharmacodynamic effects of apremilast on plasma biomarkers associated with inflammation were evaluated in a PALACE 1 substudy. Of 504 patients randomized in PALACE 1, 150 (placebo: ; apremilast 20 mg BID: ; apremilast 30 mg BID: ) provided peripheral blood plasma samples for analysis in a multiplexed cytometric bead array assay measuring 47 proteins associated with systemic inflammatory immune responses. Association between biomarker levels and achievement of 20% improvement from baseline in modified American College of Rheumatology (ACR20) response criteria was assessed by logistic regression. At Week 24, IL-8, TNF-α, IL-6, MIP-1β, MCP-1, and ferritin were significantly reduced from baseline with apremilast 20 mg BID or 30 mg BID versus placebo. ACR20 response correlated with change in TNF-α level with both apremilast doses. At Week 40, IL-17, IL-23, IL-6, and ferritin were significantly decreased and IL-10 and IL-1 receptor antagonists significantly increased with apremilast 30 mg BID versus placebo. In patients with active psoriatic arthritis, apremilast reduced circulating levels of Th1 and Th17 proinflammatory mediators and increased anti-inflammatory mediators.