Efficacy and Safety of Once‐Daily Roflumilast Cream 0.05% in Pediatric Patients Aged 2–5 Years With Mild‐to‐Moderate Atopic Dermatitis ( <scp>INTEGUMENT</scp> ‐ <scp>PED</scp> ): A Phase 3 Randomized Controlled Trial
Lawrence F. Eichenfield, Rocco Serrao, Vimal H. Prajapati, Joseph Browning, Lisa Swanson, Tracy Funk, Mercedes E. González, Adelaide A. Hebert, Mark S. Lee, Mark Boguniewicz, Eric L. Simpson, Melissa S. Seal, David Krupa, Diane Hanna, Scott Snyder, Patrick Burnett, David H. Chu, Eric L. Simpson, Robert Higham, David R. Berk
Abstract
BACKGROUND/OBJECTIVES: Efficacy and safety of roflumilast cream 0.15% were demonstrated in patients aged ≥ 6 years with atopic dermatitis (AD) in two Phase 3 trials. This Phase 3 parallel-group, double-blind trial (INTEGUMENT-PED; NCT04845620) compared the efficacy and safety of roflumilast cream 0.05% and a vehicle in patients aged 2-5 years with AD. METHODS: Patients aged 2-5 years with mild-to-moderate AD were treated with once-daily roflumilast cream 0.05% or vehicle for 4 weeks. The primary efficacy endpoint was Validated Investigator Global Assessment for AD (vIGA-AD) Success (0 [Clear] or 1 [Almost Clear] plus ≥ 2-grade improvement from baseline) at Week 4. Other endpoints included ≥ 75% improvement in Eczema Area and Severity Index (EASI-75) and Worst Itch-Numeric Rating Score (WI-NRS) Success (≥ 4-point improvement in patients with baseline ≥ 4). Safety and tolerability were also assessed. RESULTS: Among 437 and 215 patients treated with roflumilast and vehicle, respectively, significantly greater proportions of the roflumilast group achieved Week-4 vIGA-AD Success (25.4% vs. 10.7%; p < 0.0001), EASI-75 (39.4% vs. 20.6%; p < 0.0001), and WI-NRS Success (35.3% vs. 18.0%; nominal p = 0.0002). Improvement in pruritus was observed within 24 h after the first application (nominal p = 0.0014). Treatment-emergent adverse event (TEAE) rates were low in both groups, and 98.9% were mild or moderate. At all timepoints, stinging/burning that caused definite discomfort was reported by ≤ 0.7% of caregivers of patients in the roflumilast group. CONCLUSIONS: In this Phase 3 trial, once-daily roflumilast cream 0.05% improved AD signs/symptoms in patients aged 2-5 years, with early pruritus improvement, low AE rates, and local tolerability comparable with vehicle. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04845620.