Two phase 3 studies in atopic dermatitis with crisaborole, the novel, nonsteroidal topical phosphodiesterase 4 inhibitor
Background: Atopic dermatitis (AD), a chronic inflammatory skin disease affecting children and adults, presents withmild-to-moderate disease in the majority of patients (up to 90%). Crisaborole [Crisaborole Topical Ointment, 2%] (Anacor Pharmaceuticals, Palo Alto, CA) is an investigational topical, nonsteroidal, anti-inflammatory, phosphodiesterase 4 inhibitor. Objectives: To assess the efficacy and safety of crisaborole in patients ≥2 years old with mild-to-moderate AD in two identically designed, vehicle-controlled, double-blind, multicenter, Phase 3 studies (301, 302). Methods: Patients with AD affecting ≥5% of body surface area (BSA) were evaluated on Days 8 (D8), 15, 22, and 29 after being randomized 2:1 to receive crisaborole or vehicle twice daily. The primary efficacy endpoint defined Success in Investigator's Static Global Assessment (ISGA) as “Clear/0” or “Almost clear/1” with a ≥ 2-grade improvement from baseline at D29. Secondary endpoints measured time to success in ISGA and the percentage of patients achieving “Clear/0” or “Almost clear/1” on ISGA. Results: By D8, a greater proportion of crisaborole-treated patients achieved Success in ISGA than vehicle (301: 13.4 vs. 4.5, 302: 15.9 vs. 6.3), which was sustained throughout treatment (D29, 301: 32.8 vs. 25.4, p = 0.038, 302: 31.4 vs. 18.0, p < 0.001). Crisaborole-treated patients achieved success in ISGA significantly earlier (p < 0.001). A greater proportion of crisaborole-treated patients achieved ISGA scores of “Clear/0” or “Almost clear/ 1” by D29 (301: 51.7 vs. 40.6, p = 0.005; 302: 48.5 vs. 29.7, p < 0.001). Treatment-related adverse events (AEs) were infrequent, transient, and mild. AEs resulted in a low rate of study discontinuation for both groups (1.2%). Conclusion: Crisaborole may represent an efficacious and safe treatment for patients ≥2 years of age withmild-to-moderate AD.