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

Keywords

endogenous compound, phosphodiesterase IV inhibitor, roflumilast, Twist related protein 2, adult, body surface, burn, clinical trial, conference abstract, dermis, double blind procedure, drug combination, drug efficacy, drug safety, drug therapy, drug tolerability, drug withdrawal, female, human, incidence, least square analysis, major clinical study, male, numeric rating scale, phase 3 clinical trial, psoriasis, Psoriasis Area and Severity Index, psoriasis vulgaris, randomized controlled trial

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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