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

J Am Acad Dermatol. 2016 Sep;75(3):494-503.e6. doi: 10.1016/j.jaad.2016.05.046. Epub 2016 Jul 11.

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.

Keywords: atopic dermatitis; crisaborole ointment; eczema; phosphodiesterase 4; pruritus; topical therapy.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

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

Substances

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

Associated data

  • ClinicalTrials.gov/NCT02118766
  • ClinicalTrials.gov/NCT02118792