Roflumilast Cream Significantly Benefits Psoriasis Severity, Itch in Phase 3 DERMIS Trials

Investigational topical therapy roflumilast cream provided patients statistically significant improvements in plaque psoriasis symptom and disease severity outcomes versus vehicle treatment, according to new pooled findings from the phase 3 DERMIS-1 and DERMIS-2 trials.

The new findings, presented at the American Academy of Dermatology (AAD) 2022 Annual Meeting in Boston, MA, show the phosphodiesterase-4 (PDE-4) inhibitor may provide particularly significant benefit compared to available topical therapies for patients with plaque psoriasis.

Led by Mark Lebwohl, MD, of the Icahn School of Medicine at Mount Sinai, investigators assessed pooled efficacy and safety outcomes associated with roflumilast cream, derived from the DERMIS trial program. The Arcutis Biotherapeutics topical therapy is under clinical review as a once-daily, nonsteroidal therapy in plaque psoriasis and is being studied in various chronic dermatologic conditions including atopic dermatitis, seborrheic dermatitis, and scalp psoriasis.

Lebwohl and colleagues noted that approximately three-fourths of all US patients with psoriasis suffer from mild-to-moderate disease, defined as <10% body surface area (BSA) of burden. While topical therapy is considered a first-line treatment option, not one novel, nonsteroidal option has been approved for the patient population in 2 decades.

“Various topical treatments are available for chronic plaque psoriasis, such as corticosteroids, vitamin D derivatives, and calcineurin inhibitors,” they wrote. “However, there remains an unmet need for effective therapies that are safe and well-tolerated for long-term use.”

The DERMIS-1 and DERMIS-2 trials were identical phase 3, randomized, double-blinded, vehicle-controlled studies assessing once-daily roflumilast cream 0.3% in patients ≥2 years old with psoriasis BSA burden anywhere from 2% to 20%. The trials sought primary endpoints of Investigator Global Assessment (IGA) Success—defined as Clear or Almost Clear IGA status plus ≥2-grade improvement from baseline—at 8 weeks.

Secondary endpoints included intertriginous IGA (I-IGA) improvement, patients achieved 75% reduction in Psoriasis Area Severity Index (PASI-75), and Worst Itching Intensity Numerical Rating Scale (WI-NRS) improvement.

DERMIS-1 included 439 participants and DERMIS-2 included 442 participants, randomized 2:1 to either roflumilast cream or vehicle. In the pooled analysis, 576 patients received roflumilast, versus 305 receiving vehicle. Both pooled treatment arms reported similar mean patient age (47.2 and 47.9 years), sex (63.4% and 64.3% male), and race (82.3% and 82.0% White). Approximately three-fourths of both treatment arms reported a baseline IGA score of 3, deemed moderate psoriasis disease.

At week 8, 39.9% of patients treated with roflumilast achieved IGA success, versus just 6.5% on vehicle (P <.0001). Another 48.0% of patients on the therapy achieved IGA Clear or Almost Clear status at week 8, versus 9.5% of patients on vehicle (P <.0001).

Investigators additionally observed significant improvements in the roflumilast arm for all secondary endpoints, include I-IGA success (69.7% vs 16.1%; P <.01), PASI-75 (40.3% vs 6.5%; P <.0001), and WI-NRS success (68.5% vs 31.3%; P <.0001).

Regarding safety and tolerability, patients treated with roflumilast reported no serious treatment-related adverse events; 97% of all patients reported no signs of irritation from the topical creams at weeks 4 and 8. The most common treatment-emergent adverse events with roflumilast included diarrhea (3.1%), headache (2.4%), and insomnia (1.4%).

Lebwohl and colleagues concluded roflumilast cream 0.3% showed statistically significant improvements in treated patients with psoriasis across all assessed endpoints of the DERMIS trials, while also showing favorable local tolerability—a key outcome for a potential once-daily topical agent.

“The pooled results of the phase 3 DERMIS-1 and DERMIS-2 studies demonstrated that investigational, once-daily roflumilast cream 0.3% has the potential to address many of the shortcomings of existing topical treatments for plaque psoriasis,” they wrote.

The study, “Pooled Efficacy and Safety Results From the DERMIS-1 and DERMIS-2 Phase 3 Trials of Once-Daily Roflumilast Cream 0.3% for Treatment of Chronic Plaque Psoriasis,” was presented at AAD 2022.