Two phase 3 studies in atopic dermatitis with crisaborole, the novel, nonsteroidal topical phosphodiesterase 4 inhibitor
Paller A, Tom W, Lebwohl M, Blumenthal R, Boguniewicz M, Call R, Eichenfield L, Forsha D, Rees W, Simpson E, Stein Gold LF, Zaenglein A, Spellman M, Zane L, Hebert A. Two phase 3 studies in atopic dermatitis with crisaborole, the novel, nonsteroidal topical phosphodiesterase 4 inhibitor. Pediatr Dermatol 2016; 33(Suppl 1):S19.
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.