Reduction in Pruritus Across Indications in Phase 3 Trials of Topical Roflumilast
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Keywords
topical roflumilast, seborrheic dermatitis, atopic dermatitis, psoriasis, itch, pruritus
Abstract
Background: Pruritus is a burdensome symptom affecting quality of life (QOL) in patients with seborrheic dermatitis (SD), psoriasis, and atopic dermatitis (AD). Phosphodiesterase4 (PDE4) inhibitors may reduce pruritus by reducing inflammatory itch mediators. Topical roflumilast, formulated as a water-based foam or cream without penetration enhancers or fragrances, is a selective, highly potent PDE4 inhibitor. Efficacy and safety of once-daily, topical roflumilast has been demonstrated in patients with psoriasis (cream 0.3% and foam 0.3%), SD (foam 0.3%), and AD (0.15% and 0.05% cream).
Methods: Itch response was evaluated in phase 3 clinical trials of roflumilast in patients aged ≥9 years with SD (STRATUM) or ≥12 years with psoriasis (DERMIS-1, DERMIS-2, ARRECTOR) and patients aged ≥6 years with AD (INTEGUMENT-1, INTEGUMENT-2). Patients were randomized to apply topical roflumilast (DERMIS: 0.3% cream; ARRECTOR and STRATUM: 0.3% foam; INTEGUMENT: 0.15% cream) or vehicle (cream or foam) once daily for 8 weeks (DERMIS, ARRECTOR, and STRATUM) 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]).
Results: More roflumilast- versus vehicle-treated patients achieved WI-NRS success (≥4-point improvement in patients with baseline score ≥4) at the final assessment: STRATUM: 62.8% vs 40.6%; DERMIS: 68.5% vs 31.3%; ARRECTOR: 63.1% vs 30.1%; INTEGUMENT: 31.9% vs 16.6%, respectively (all P<0.0001). Differences favoring roflumilast versus vehicle were also observed for achievement of WI-NRS 0/1 (in patients with baseline score ≥2) after the first or second application (STRATUM, ARRECTOR, INTEGUMENT; all nominal P<0.05) and at final assessment: STRATUM: 70.7% vs 52.9%; DERMIS: 55.4% vs 19.4%; ARRECTOR: 55.4% vs 19.8%; INTEGUMENT: 28.8% vs 18.5%, respectively (all nominal P<0.01).
Conclusions: Once-daily topical roflumilast provided consistent and rapid improvements in itch across SD, psoriasis, and AD, highlighting roflumilast’s potential to reduce this burdensome symptom and improve QOL across indications.
Sponsored by Arcutis Biotherapeutics, Inc.
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