(102) Caregiver-reported outcomes from the phase 3 INTEGUMENT-PED trial of children aged 2–5 years with atopic dermatitis and treated with roflumilast cream 0.05%

Background: : Poorly controlled AD may impact the whole family. Roflumilast (ROF) cream 0.15% and 0.05% have demonstrated efficacy, safety, and tolerability, compared with vehicle (VEH), in patients with atopic dermatitis (AD) in the INTEGUMENT-1/2 (aged ≥6 years) and INTEGUMENT-PED (aged 2–5 years) phase 3 trials, respectively.

Objective: : Evaluate changes in symptoms and patient-reported outcomes (PRO) with ROF versus VEH in patients from INTEGUMENT-PED/NCT04845620.

Methods: : Eligible patients were aged 2–5 years with mild to moderate AD. ROF cream 0.05% or VEH cream was applied once daily by a caregiver for 4 weeks. The primary endpoint was Validated Investigator Global Assessment for AD (vIGA-AD) success (clear/almost clear [0/1] plus ≥2-grade improvement from baseline) at week 4. PROs reported by caregivers included Worst Itch-Numeric Rating Score (WI-NRS) success (≥4-point improvement in patients with baseline score ≥4), SCORing AD (SCORAD), Patient-Oriented Eczema Measure (POEM), Children’s Dermatology Life Quality Index (CDLQI; aged ≥4 years), Infant DLQI (IDLQI; aged < 4 years), and the Dermatitis Family Impact questionnaire (DFI).

Results: : After 4 weeks, significantly greater proportions of patients randomized to ROF (n=437) versus VEH (n=215) achieved vIGA-AD success (25.4% vs 10.7%; P< 0.0001) and WI-NRS success (35.3% [97.5% CI, 29.7–41.4] vs 18.0% [12.0–26.1]; P< 0.0002). Least-squares mean (LSM) improvement in SCORAD from baseline to week 4 was significantly greater for the ROF versus VEH group overall (19.30 vs 12.30; P< 0.0001) and for individual components of pruritus (3.11 vs 1.85; P< 0.0001), sleep loss (2.05 vs 1.29; P=0.0005), and dryness (0.59 vs 0.43; P=0.0061). Significant improvements (all P< 0.05) with ROF versus VEH occurred for POEM overall (7.5 vs 3.7) and individual component scores (itching, 1.30 vs 0.73; sleep, 1.01 vs 0.60; skin bleeding, 0.91 vs 0.55; skin weeping/oozing, 0.40 vs 0.25; skin cracking, 1.35 vs 0.60; skin flaking, 1.19 vs 0.54; dryness/roughness, 1.47 vs 0.60). Compared with VEH, ROF significantly improved (LSM change from baseline) CDLQI (5.2 vs 3.2; P=0.0031), IDLQI (4.2 vs 2.1; P< 0.0001), and DFI (4.2 vs 2.9; P=0.0015). Safety and application-site tolerability profiles of ROF cream 0.05% were favorable.

Conclusions: : Once-daily ROF cream 0.05% significantly improved AD as measured by multiple PROs, compared with VEH cream, after 4 weeks of treatment in patients aged 2–‍5 years with AD, consistent with outcomes reported for patients aged ≥6 years with AD.

Sponsorship:: Arcutis Biotherapeutics, Inc.