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

Abstract

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.

• Authors: Bruce Strober, Ali Alikhan, Benjamin Lockshin, Rebecca Shi, Joshua Cirulli, Peter Schafer
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 96 Issue 3 Pg. 126-133 (Dec 2019) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 31787506 (Publication Type: Clinical Trial, Phase IV, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.

Chemical References

• Adipokines
• Anti-Inflammatory Agents, Non-Steroidal
• Apolipoproteins
• Cytokines
• Thalidomide
• apremilast

Topics

• Adipokines (blood)
• Adult
• Aged
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Apolipoproteins (blood)
• Cytokines (blood)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Psoriasis (blood, drug therapy, immunology)
• T-Lymphocyte Subsets
• Thalidomide (analogs & derivatives, pharmacology, therapeutic use)