Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults.

Abstract

BACKGROUND:

Additional topical treatments for atopic dermatitis (AD) are needed that provide relief while minimizing risks.

OBJECTIVE:

We sought to assess the efficacy and safety of crisaborole ointment, a phosphodiesterase 4 inhibitor, in two phase III AD studies (AD-301: NCT02118766; AD-302: NCT02118792).

METHODS:

Two identically designed, vehicle-controlled, double-blind studies enrolled and randomly assigned (2:1, crisaborole:vehicle) patients aged 2 years or older with an Investigator's Static Global Assessment (ISGA) score of mild or moderate for twice-daily application for 28 days. The primary end point was ISGA score at day 29 of clear (0)/almost clear (1) with 2-grade or greater improvement from baseline. Additional analyses included time to success in ISGA score, percentage of patients achieving clear/almost clear, reduction in severity of AD signs, and time to improvement in pruritus.

RESULTS:

More crisaborole- than vehicle-treated patients achieved ISGA score success (clear/almost clear with ≥2-grade improvement; AD-301: 32.8% vs 25.4%, P = .038; AD-302: 31.4% vs 18.0%, P < .001), with a greater percentage with clear/almost clear (51.7% vs 40.6%, P = .005; 48.5% vs 29.7%, P < .001). Crisaborole-treated patients achieved success in ISGA score and improvement in pruritus earlier than those treated with vehicle (both P ≤ .001). Treatment-related adverse events were infrequent and mild to moderate in severity.

LIMITATIONS:

Short study duration was a limitation.

CONCLUSIONS:

Crisaborole demonstrated a favorable safety profile and improvement in all measures of efficacy, including overall disease severity, pruritus, and other signs of AD.

• Authors: Amy S Paller, Wynnis L Tom, Mark G Lebwohl, Robin L Blumenthal, Mark Boguniewicz, Robert S Call, Lawrence F Eichenfield, Douglass W Forsha, William C Rees, Eric L Simpson, Mary C Spellman, Linda F Stein Gold, Andrea L Zaenglein, Matilda H Hughes, Lee T Zane, Adelaide A Hebert
• Journal: Journal of the American Academy of Dermatology (J Am Acad Dermatol) Vol. 75 Issue 3 Pg. 494-503.e6 (Sep 2016) ISSN: 1097-6787 [Electronic] United States
• PMID: 27417017 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Boron Compounds
• Bridged Bicyclo Compounds, Heterocyclic
• Dermatologic Agents
• Ointments
• Cyclic Nucleotide Phosphodiesterases, Type 4
• crisaborole

Topics

• Administration, Cutaneous
• Adolescent
• Adult
• Aged
• Boron Compounds (adverse effects, therapeutic use)
• Bridged Bicyclo Compounds, Heterocyclic (adverse effects, therapeutic use)
• Child
• Child, Preschool
• Cyclic Nucleotide Phosphodiesterases, Type 4 (adverse effects, therapeutic use)
• Dermatitis, Atopic (complications, drug therapy)
• Dermatologic Agents (adverse effects, therapeutic use)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Ointments
• Pruritus (drug therapy, etiology)
• Young Adult