title: 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).
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: n = 51; apremilast 20 mg BID: n = 51; apremilast 30 mg BID: n = 48) 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.
authors.affiliation: Translational Development, Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Schafer
authors.affiliation: Biostatistics, Celgene Corporation, 33 Technology Drive, Warren, NJ 07059, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Biostatistics, Celgene Corporation, 33 Technology Drive, Warren, NJ 07059, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Fang
authors.affiliation: Biostatistics, Celgene Corporation, 33 Technology Drive, Warren, NJ 07059, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wang
authors.affiliation: Translational Development, Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Chopra
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000097:blood* / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood*; D016207:Cytokines / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D058988:Phosphodiesterase 4 Inhibitors / Q000627:therapeutic use*; D010919:Placebos; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D016207:Cytokines; D058988:Phosphodiesterase 4 Inhibitors; D010919:Placebos; D013792:Thalidomide; C505730:apremilast