Safety and efficacy of once-daily roflumilast cream 0.3%, a potent phosphodiesterase-4 inhibitor, for the treatment of psoriasis in the DERMIS-1 and DERMIS-2 Phase 3 trials

Document Type

Conference Proceeding

Publication Date

5-27-2022

Publication Title

J Clin Aesthet Dermatol

Abstract

Background: Roflumilast cream 0.3%, a selective and highly potent phosphodiesterase-4 inhibitor, is being investigated as a nonsteroidal, once-daily treatment for long-term management of psoriasis. We describe the effects of once-daily roflumilast cream 0.3% on plaque psoriasis during two Phase 3, randomized, double-blind, vehicle-controlled, multi-center trials. Methods: DERMIS-1 (N=439; NCT04211363) and DERMIS-2 (N=442; NCT04211389) were identical Phase 3 trials conducted in patients (>2 years) with psoriasis involving 2-20% of body surface area (BSA). Patients were randomized 2:1 to once-daily roflumilast cream 0.3% or vehicle for eight weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) Success (IGA status of Clear or Almost Clear plus >2-grade improvement from baseline) at Week 8. Results: In both studies, significantly more roflumilast-treated patients than vehicle-treated patients achieved IGA Success (DERMIS-1: 42.4% vs. 6.1%; DERMIS-2: 37.5% vs 6.9%, P<0.001 for both) at Week 8. Statistically significant differences favoring roflumilast were observed for multiple secondary endpoints, including percentage of patients achieving intertriginous-IGA Success (DERMIS-1: 71.2% vs. 13.8%; DERMIS-2: 68.1% vs. 18.5%, P<0.01), percentage of patients achieving 75% reduction in Psoriasis Area Severity Index (DERMIS-1: 41.6% vs. 7.6%; DERMIS-2: 39.0% vs 5.3%, P<0.0001), percentage of patients achieving 90% reduction in Psoriasis Area Severity Index (DERMIS-1: 22.4% vs. 2.3%; DERMIS-2: 17.0% vs 2.3%, P<0.0001), and percentage of patients with baseline Worst Itch-Numeric Rating Scale ≥4 achieving a 4-point reduction in WI-NRS (DERMIS-1: 67.5% vs 26.8%; DERMIS-2: 69.4% vs 35.6%, P<0.0001) at Week 8. Roflumilast also demonstrated superior improvement from baseline in BSA compared with vehicle at Weeks 2-8 (P<0.01). The improvements in investigatorassessed disease severity were consistent with improvements in patient-reported disease severity and burden as indicated by a significantly greater reduction in total Psoriasis Symptom Diary score compared with vehicle-treated patients. At Week 8, least square mean difference in percentage change from baseline total PSD score compared with vehicle treatment was -54.3% in DERMIS-1 and -38.8% in DERMIS-2 (P<0.001). Local tolerability was highly favorable as reported by patient and investigator assessment of irritation, burning, and stinging. On investigator-rated local tolerability, over 96 percent of patients in each group had no evidence of irritation at Week 4 or Week 8. On patient-rated local tolerability, scores were low (favorable) and similar to vehicle at all timepoints. Overall incidence of treatment-emergent adverse events (TEAE), serious adverse events, and TEAEs leading to discontinuation were low with similar rates between roflumilast and vehicle across both studies. Conclusion: Results from these two Phase 3 studies indicate that roflumilast cream 0.3% demonstrated superior improvement across multiple efficacy endpoints versus vehicle cream with onset as early as 2 weeks and was well-tolerated with low rates of application site and treatment-related AEs in patients with psoriasis.

Volume

15

Issue

4 SUPPL 1

First Page

S33

Last Page

S45

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