BACKGROUND: Pharmacodynamic (PD) subanalyses of clinical trials in patients with moderate to severe psoriasis demonstrated the efficacy of apremilast correlated with reductions in cytokines involved in the pathogenesis of psoriasis. OBJECTIVE: This PD subanalysis of a phase IV, randomized, controlled trial (UNVEIL) in systemic-naive patients with moderate plaque psoriasis (psoriasis-involved body surface area [BSA] 5%-10%; static Physician's Global Assessment [sPGA] = 3) evaluated the relationship between efficacy and changes in inflammatory biomarkers with apremilast 30 mg twice daily (BID) versus placebo. METHODS: Patients were randomized (2:1) to apremilast 30 mg BID or placebo for 16 weeks. Blood samples were analyzed for interleukins (IL)-17A, -17F, -22, and -23; cardiometabolic biomarkers (leptin; adiponectin; apolipoproteins A-I, A-II, B, and E); and the number of T-helper 17 (Th17) cells, regulatory T cells, and total T cells at Weeks 0, 4, and 16. Correlations were examined between percentage change in biomarkers and efficacy (based on PGAxBSA). RESULTS: Of 221 randomized patients, 38 were included in PD analyses (placebo, n = 12; apremilast, n = 26). Median percentage reductions in plasma cytokine levels were significantly greater with apremilast versus placebo for IL-17A (P < 0.05), IL -17F (P < 0.001), and IL-22 (P < 0.01) at Week 4 and IL-22 (P < 0.05) at Week 16. At Week 16, in patients receiving apremilast, improvement in PGAxBSA significantly correlated with change in IL-17A (r = 0.45, P = 0.04). Adipokines, apolipoproteins, and T-cell population levels were largely unchanged. CONCLUSION: Clinical improvements in psoriasis correlated with apremilast-mediated decreases in IL-17A without significantly affecting systemic IL-23 levels, adipokines, or Th17 and regulatory T-cell numbers.