Apremilast mechanism of efficacy in systemic-naive patients with moderate plaque psoriasis: Pharmacodynamic results from the UNVEIL study.

Abstract

BACKGROUND\nPharmacodynamic (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.\n\n\nOBJECTIVE\nThis 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]\u202f=\u202f3) evaluated the relationship between efficacy and changes in inflammatory biomarkers with apremilast 30\u202fmg twice daily (BID) versus placebo.\n\n\nMETHODS\nPatients were randomized (2:1) to apremilast 30\u202fmg 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).\n\n\nRESULTS\nOf 221 randomized patients, 38 were included in PD analyses (placebo, n\u202f=\u202f12; apremilast, n\u202f=\u202f26). Median percentage reductions in plasma cytokine levels were significantly greater with apremilast versus placebo for IL-17A (P\u202f<\u202f0.05), IL -17F (P\u202f<\u202f0.001), and IL-22 (P\u202f<\u202f0.01) at Week 4 and IL-22 (P\u202f<\u202f0.05) at Week 16. At Week 16, in patients receiving apremilast, improvement in PGAxBSA significantly correlated with change in IL-17A (r\u202f=\u202f0.45, P\u202f=\u202f0.04). Adipokines, apolipoproteins, and T-cell population levels were largely unchanged.\n\n\nCONCLUSION\nClinical 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.