Reduction in Pruritus Across Indications in Phase 3 Trials of Topical Roflumilast in Patients as Young as 2 Years

Abstract

Pruritus is a burdensome symptom affecting quality of life in patients with seborrheic dermatitis (SebDerm), psoriasis (PsO), and atopic dermatitis (AD). Phosphodiesterase 4 (PDE4) inhibitors may improve pruritus by reducing inflammatory itch mediators. Topical roflumilast is a selective, highly potent PDE4 inhibitor formulated as a water-based foam or cream without propylene glycol, formaldehyde, fragrances, or other potentially irritating excipients. Efficacy and safety of once-daily, topical roflumilast was demonstrated in patients with SebDerm aged ≥9 years (foam 0.3%), PsO aged ≥2 years (cream 0.3%), PsO of the scalp and body aged ≥12 years (foam 0.3%), and mild-to-moderate AD aged ≥6 years (cream 0.15%) or 2–5 years (cream 0.05%). Patients were randomized to apply topical roflumilast or vehicle once daily for 8 weeks (STRATUM, DERMIS, ARRECTOR) or 4 weeks (INTEGUMENT). Patients rated their itch daily (STRATUM, ARRECTOR, INTEGUMENT) or at regularly scheduled visits (DERMIS) according to the Worst Itch-Numeric Rating Scale (WI-NRS; ranging from 0 [no itch] to 10 [worst itch imaginable]). Higher proportions of patients in the roflumilast versus vehicle group achieved WI-NRS success (≥4-point improvement in patients with baseline score ≥4) at the final assessment: STRATUM: 62.8% vs 40.6%; DERMIS-1/2 (≥12 years): 68.5% vs 31.3%; ARRECTOR: 63.1% vs 30.1%; INTEGUMENT-1/2: 34.4% vs 15.9%; INTEGUMENT-PED: (35.3% vs 18.0%), respectively (all P≤0.0002). Differences favoring roflumilast versus vehicle were observed for daily itch score after the first or second application (all but DERMIS-1/2) and achievement of WI‑NRS 0/1 at final assessment (in patients with baseline score ≥2): STRATUM: 70.7% vs 52.9%; DERMIS‑1/2 (≥12 years): 55.4% vs 19.4%; ARRECTOR: 55.4% vs 19.8%; INTEGUMENT-1/2 (≥12 years): 28.8% vs 18.5%; INTEGUMENT-PED: 23.0% vs 7.8%, respectively (all nominal P<0.01). Once-daily topical roflumilast provided consistent and rapid improvements in itch across SebDerm, PsO, and AD, highlighting roflumilast’s potential to reduce this burdensome symptom and improve quality of life across indications. Sponsored by Arcutis Biotherapeutics, Inc.