Efficacy and safety of roflumilast cream 0.15% in adults and children aged=6 years with mild to moderate atopic dermatitis in two phase 3 trials (INTEGUMENT-1 and INTEGUMENT-2)

Abstract Roflumilast is a selective, highly potent phosphodie­sterase 4 inhibitor under investigation as a nonsteroidal, once-daily cream for treatment of atopic dermatitis (AD). INTEGUMENT-1 (n = 654; NCT04773587) and INTEGUMENT-2 (n = 683; NCT04773600) were identical phase 3 randomized controlled trials conducted in patients with AD aged ≥6 years with baseline Eczema Area and Severity Index (EASI) score ≥5 and Validated Investigator Global Assessment-AD (vIGA-AD) score of mild or moderate. Patients were randomized 2 : 1 to apply once-daily roflumilast cream 0.15% or vehicle for 4 weeks. The primary efficacy endpoint was vIGA-AD Success [defined as score of 0 (clear) or 1 (almost clear) with 2-grade improvement from baseline] at Week 4. Secondary endpoints included 75% improvement in EASI (EASI-75). At Week 4, significantly more roflumilast-treated than vehicle-treated patients achieved vIGA-AD Success (INTEGUMENT-1: 32.2% vs. 15.2%; P < 0.0001; INTEGUMENT-2: 28.9% vs. 12.0%; P < 0.0001) and EASI-75 (INTEGUMENT-1: 43.2% vs. 22.0%; P < 0.0001; INTEGUMENT-2: 42.0% vs. 19.7%; P < 0.0001). Incidence of treatment-emergent adverse events (AEs) was low in both arms, with most assessed as mild to moderate in severity. No AE occurred in more than 3.5% of patients in either arm with low rates of application site pain in both the roflumilast- and vehicle-treated patients (INTEGUMENT-1: 2.1% vs. 0.5%; INTEGUMENT-2: 0.9% vs. 0.9%). Local tolerability was favorable with >90% of roflumilast-treated patients reporting no or mild sensation across arms in both trials at any timepoint. Once-daily roflumilast cream 0.15% improved AD across multiple efficacy endpoints while demonstrating favorable safety and tolerability in two phase 3 trials.