Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1).

Abstract

BACKGROUND:

Apremilast works intracellularly to regulate inflammatory mediators.

OBJECTIVE:

ESTEEM 1 evaluated efficacy/safety of apremilast at 30 mg twice a day for moderate to severe plaque psoriasis.

METHODS:

This phase III, multicenter, double-blind, placebo-controlled study randomized adults (2:1) to apremilast or placebo. At week 16, the placebo group switched to apremilast through week 32, followed by a randomized treatment withdrawal phase to week 52. Binary end points were analyzed using χ(2) test; continuous end points used analysis of covariance.

RESULTS:

In all, 844 patients were randomized (n = 282, placebo; n = 562, apremilast). At week 16, significantly more patients taking apremilast achieved 75% or greater reduction from baseline Psoriasis Area and Severity Index score (PASI-75) (33.1%) versus placebo (5.3%, P < .0001; primary end point). Most (61.0%) patients rerandomized to apremilast at week 32 achieved PASI-75 at week 52 versus 11.7% rerandomized to placebo. Of patients rerandomized to apremilast at week 32, mean percentage change from baseline PASI score was -88% to -81% (weeks 32-52). During the placebo-controlled period, 55.7% and 69.3% of patients randomized to placebo and apremilast, respectively, had 1 or more adverse events. Most adverse events were mild/moderate in severity. No new significant adverse events emerged with continued apremilast exposure versus the placebo-controlled period.

LIMITATIONS:

Data were limited to 52 weeks and may not generalize to nonplaque psoriasis.

CONCLUSIONS:

Apremilast was effective in moderate to severe plaque psoriasis.

• Authors: Kim Papp, Kristian Reich, Craig L Leonardi, Leon Kircik, Sergio Chimenti, Richard G B Langley, ChiaChi Hu, Randall M Stevens, Robert M Day, Kenneth B Gordon, Neil J Korman, Christopher E M Griffiths
• Journal: Journal of the American Academy of Dermatology (J Am Acad Dermatol) Vol. 73 Issue 1 Pg. 37-49 (Jul 2015) ISSN: 1097-6787 [Electronic] United States
• PMID: 26089047 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Phosphodiesterase 4 Inhibitors
• Thalidomide
• apremilast

Topics

• Administration, Oral
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Phosphodiesterase 4 Inhibitors (administration & dosage)
• Psoriasis (drug therapy)
• Severity of Illness Index
• Thalidomide (administration & dosage, analogs & derivatives)