Roflumilast Cream, a Once-daily, Potent Phosphodiesterase-4 Inhibitor, in Chronic Plaque Psoriasis Patients: Efficacy and Safety from DERMIS-1 and DERMIS-2 Phase 3 Trials

Document Type

Conference Proceeding

Publication Date

10-27-2021

Publication Title

J Cutan Med Surg

Keywords

endogenous compound, roflumilast, steroid, Twist related protein 2, adult, application site pain, body surface, clinical trial, conference abstract, controlled study, dermis, double blind procedure, drug efficacy, drug safety, drug therapy, drug tolerability, drug withdrawal, female, human, incidence, learning, major clinical study, male, numeric rating scale, outcome assessment, patient-reported outcome, pharmacokinetics, phase 3 clinical trial, Psoriasis Area and Severity Index, psoriasis vulgaris, randomized controlled trial

Abstract

Introduction: Novel nonsteroidal topical therapies for psoriasis have not been approved in over 20 years. Recent data suggest roflumilast 0.3% cream, a potent phosphodiester ase-4 inhibitor, may represent a highly-effective, well-tolerated, nonsteroidal, once-daily treatment for long-term management of chronic plaque psoriasis, including the face and intertriginous areas. Methods, Results: Two identical Phase 3, randomized, double-blind, vehicle-controlled, multi-center trials (DERMIS-1 [n = 439; NCT04211363] and DERMIS-2 [n = 442; NCT04211389]) were conducted in patients ≥2 years old with chronic plaque psoriasis involving 2%-20% of body surface area. Patients were randomized 2:1 to receive roflumilast cream 0.3% or vehicle once-daily for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) success at Week 8. Significantly more roflumilast-treated patients reached IGA success (DERMIS-1: 42.4%; DERMIS-2: 37.5%) than vehicle-treated patients (DERMIS-1: 6.1%; DERMIS-2: 6.9%, P < 0.001 for both). In patients with intertriginous area involvement, significantly more roflumilast-treated patients reached intertriginous-IGA (I-IGA) success at week 8 than vehicle-treated (DERMIS-1: 71.2% vs. 13.8%, P < 0.0001; DERMIS-2: 68.1% vs 18.5%, P = 0.0004). A majority of these patients achieved I-IGA=0. Approximately 40% of patients achieved 75% reduction in Psoriasis Area Severity Index (PASI 75) by week 8 (DERMIS-1: 41.6% vs. 7.6%; DERMIS-2: 39.0% vs 5.3%, P < 0.0001). Patients with baseline Worst Itch-Numeric Rating Scale (WI-NRS) ≥4 achieved a 4-point reduction in WI-NRS at week 8 (DERMIS-1: 67.5% vs 26.8%; DERMIS-2: 69.4% vs 35.6%, P < 0.0001). Itch improvement was notable by 2 weeks, the earliest timepoint measured (DERMIS-2: P = 0.0026). Incidence of treatment-emergent adverse events (TEAE) were low and similar between roflumilast and vehicle groups. Pooled rates of TEAE leading to discontinuation (1.0% roflumilast vs 1.3% vehicle) and application site pain (1.0% roflumilast vs 0.3% vehicle) were low and comparable to vehicle. Conclusions: Roflumilast cream 0.3% demonstrated favorable safety and tolerability while delivering statistically superior efficacy vs vehicle across multiple endpoints in patients with chronic plaque psoriasis. Learning Objective To learn about the Phase 3 data demonstrating the efficacy, safety, and tolerability of once-daily, non-steroidal, roflumilast 0.3% cream, a potent PDE4 inhibitor, developed for the treatment of chronic plaque psoriasis To highlight the burdensome patient-reported outcome of itch in patients with chronic plaque psoriasis and the ability of once-daily roflumilast 0.3% cream to reduce itch. To learn about the efficacy and tolerability for intertriginous plaques demonstrating the ability to use roflumilast cream in these steroid-sensitive areas. Takeaway Message In two phase 3 studies, once-daily roflumilast cream 0.3% demonstrated favorable safety and tolerability while effectively improving chronic plaque psoriasis and burdensome signs and symptoms, such as itch.

Volume

25

Issue

1 SUPPL

First Page

78S

Last Page

79S

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