Faculty Collaboration Database

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). J Am Acad Dermatol 2015 Jul;73(1):37-49

Date

06/20/2015

Pubmed ID

26089047

DOI

10.1016/j.jaad.2015.03.049

Scopus ID

2-s2.0-84937880965 (requires institutional sign-in at Scopus site)   471 Citations

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.

Author List

Papp K, Reich K, Leonardi CL, Kircik L, Chimenti S, Langley RG, Hu C, Stevens RM, Day RM, Gordon KB, Korman NJ, Griffiths CE

Author

Kenneth Brian Gordon MD Chair, Professor in the Dermatology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Administration, Oral
Double-Blind Method
Female
Humans
Male
Middle Aged
Phosphodiesterase 4 Inhibitors
Psoriasis
Severity of Illness Index
Thalidomide