Aim: To assess the efficacy and safety of crisaborole ointment, a phosphodiesterase 4 inhibitor, for the treatment of mild or moderate atopic dermatitis (AD) in two phase III studies (AD-301 and AD-302).
Design and setting: Two identically designed multicentre, double-blind randomized controlled trials were conducted in the U.S.A. Participants were randomized 2 : 1 to receive crisaborole or vehicle treatment. In total 47 and 42 investigational centres were identified for AD-301 and AD-302, respectively.
Study participants: Inclusion criteria were identified as age ≥ 2 years, clinical diagnosis of AD (as per the Hanifin and Rajka criteria), ≥ 5% body surface area involvement, and baseline Investigator's Static Global Assessment (ISGA) mild or moderate. Exclusion criteria included previous use of biologics or systemic corticosteroids (within the last 28 days) or a topical calcineurin inhibitor/corticosteroid (within the last 14 days), and active skin infection.
Exposures: Participants were instructed to apply the study drug twice daily to all lesions identified at baseline, and all new lesions identified after day 1 (with weekly review of application instructions). Bland emollients were permitted to be used on skin not treated with the study drug.
Primary outcome: The primary outcome was defined as ISGA clear or almost clear at day 29, with a 2-grade or more improvement from baseline.
Outcomes: Secondary outcomes included the proportion of patients with an ISGA score of clear or almost clear at day 29, and time to success in ISGA score. Additional outcomes included pruritus severity and signs of AD (erythema, exudation, excoriation, induration/papulation and lichenification), and were measured on a 4-point scale (none, mild, moderate, severe). Adverse events were also recorded.
Results: More participants in the crisaborole-treated group achieved ISGA scores of clear or almost clear with ≥ 2-grade improvement than in the vehicle-treated group (AD-301, 32·8% vs. 25·4%, P = 0·38; AD-302, 31·4% vs. 18·0%, P < 0·001). Greater percentages of clear and almost clear scores were observed in the treatment groups (51·7% vs. 40·6%, P = 0·005; 48·5% vs. 29·7%; P < 0·001), as well as earlier success in ISGA score and improvement in pruritus (P ≤ 0·001). No serious treatment-related adverse events were identified.
Conclusions: Based on the study results, the authors suggest that crisaborole is a safe treatment that improves disease severity, pruritus and clinical signs associated with AD.
© 2017 British Association of Dermatologists.