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Original Investigation
September 20, 2022

Effect of Roflumilast Cream vs Vehicle Cream on Chronic Plaque Psoriasis: The DERMIS-1 and DERMIS-2 Randomized Clinical Trials

Author Affiliations
  • 1Icahn School of Medicine at Mount Sinai, New York, New York
  • 2Indiana Medical Center, Indianapolis
  • 3Physicians Skin Care PLLC, Louisville, Kentucky
  • 4Skin Sciences PLLC, Louisville, Kentucky
  • 5Arlington Research Center, Arlington, Texas
  • 6Baylor University Medical Center, Dallas, Texas
  • 7Henry Ford Medical Center, Detroit, Michigan
  • 8Dermatology Consulting Services, High Point, North Carolina
  • 9SkiN Centre for Dermatology, Peterborough, Ontario, Canada
  • 10Probity Medical Research, Peterborough, Ontario, Canada
  • 11Queen’s University, Peterborough, Ontario, Canada
  • 12Probity Medical Research, Waterloo, Ontario, Canada
  • 13K Papp Clinical Research, Waterloo, Ontario, Canada
  • 14Psoriasis Treatment Center of Central New Jersey, East Windsor
  • 15Therapeutics Clinical Research, San Diego, California
  • 16JDR Dermatology Research Center LLC, Las Vegas, Nevada
  • 17Advanced Dermatology and Cosmetic Surgery, Maitland, Florida
  • 18University of Pittsburgh Clinical and Translational Science Institute, Pittsburgh, Pennsylvania
  • 19George Washington University School of Medicine, Rockville, Maryland
  • 20UT Health McGovern Medical School, Houston, Texas
  • 21US Dermatology Partners Bryan, Bryan, Texas
  • 22Minnesota Clinical Study Center, Fridley
  • 23Eastern Virginia Medical School, Norfolk
  • 24Virginia Clinical Research Inc, Norfolk
  • 25David Geffen School of Medicine at UCLA, Los Angeles, California
  • 26Dermatology Institute and Skin Care Center Inc, Santa Monica, California
  • 27Dermatologists of the Central States, Bexley, Ohio
  • 28Probity Medical Research, Bexley, Ohio
  • 29Ohio University, Bexley, Ohio
  • 30Enverus Medical Research, Surrey, British Columbia, Canada
  • 31Probity Medical Research, Surrey, British Columbia, Canada
  • 32Dermatology Research Institute, Calgary, Alberta, Canada
  • 33Probity Medical Research, Calgary, Alberta, Canada
  • 34DermEdge Research, Mississauga, Ontario, Canada
  • 35Probity Medical Research, Mississauga, Ontario, Canada
  • 36Arcutis Biotherapeutics Inc, Westlake Village, California
JAMA. 2022;328(11):1073-1084. doi:10.1001/jama.2022.15632
Key Points

Question  What is the efficacy of once-daily roflumilast cream, 0.3%, in patients with plaque psoriasis?

Findings  In 2 phase 3 randomized clinical trials with 881 participants combined, Investigator Global Assessment success at 8 weeks in the group treated with roflumilast cream vs vehicle cream was 42.4% vs 6.1% in one trial and 37.5% vs 6.9% in the other trial. Both differences were statistically significant.

Meaning  Roflumilast cream resulted in better chronic plaque psoriasis clinical status compared with vehicle cream at 8 weeks; further research is needed to compare efficacy with other active treatments and to assess longer-term efficacy and safety.

Abstract

Importance  Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis.

Objective  To evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis.

Design, Setting, and Participants  Two phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n = 439] and DERMIS-2 [trial 2; n = 442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between December 9, 2019, and November 23, 2020, respectively. Patients aged 2 years or older with plaque psoriasis involving 2% to 20% of body surface area were enrolled. The dates of final follow-up were November 20, 2020, and November 23, 2020, for trial 1 and trial 2, respectively.

Interventions  Patients were randomized 2:1 to receive roflumilast cream, 0.3% (trial 1: n = 286; trial 2: n = 290), or vehicle cream (trial 1: n = 153; trial 2: n = 152) once daily for 8 weeks.

Main Outcomes and Measures  The primary efficacy end point was Investigator Global Assessment (IGA) success (clear or almost clear status plus ≥2-grade improvement from baseline [score range, 0-4]) at week 8, analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA score, and intertriginous involvement. There were 9 secondary outcomes, including intertriginous IGA success, 75% reduction in Psoriasis Area and Severity Index (PASI) score, and Worst Itch Numeric Rating Scale score of 4 or higher at baseline achieving 4-point reduction (WI-NRS success) at week 8 (scale: 0 [no itch] to 10 [worst imaginable itch]; minimum clinically important difference, 4 points).

Results  Among 881 participants (mean age, 47.5 years; 320 [36.3%] female), mean IGA scores in trial 1 were 2.9 [SD, 0.52] for roflumilast and 2.9 [SD, 0.45] for vehicle and in trial 2 were 2.9 [SD, 0.48] for roflumilast and 2.9 [SD, 0.47]) for vehicle. Statistically significantly greater percentages of roflumilast-treated patients than vehicle-treated patients had IGA success at week 8 (trial 1: 42.4% vs 6.1%; difference, 39.6% [95% CI, 32.3%-46.9%]; trial 2: 37.5% vs 6.9%; difference, 28.9% [95% CI, 20.8%-36.9%]; P < .001 for both). Of 9 secondary end points, statistically significant differences favoring roflumilast vs vehicle were observed for 8 in trial 1 and 9 in trial 2, including intertriginous IGA success (71.2% vs 13.8%; difference, 66.5% [95% CI, 47.1%-85.8%] and 68.1% vs 18.5%; difference, 51.6% [95% CI, 29.3%-73.8%]; P < .001 for both), 75% reduction in PASI score (41.6% vs 7.6%; difference, 36.1% [95% CI, 28.5%-43.8%] and 39.0% vs 5.3%; difference, 32.4% [95% CI, 24.9%-39.8%]; P < .001 for both), WI-NRS success (67.5% vs 26.8%; difference, 42.6% [95% CI, 31.3%-53.8%] and 69.4% vs 35.6%; difference, 30.2% [95% CI, 18.2%-42.2%]; P < .001 for both). The incidence of treatment-emergent adverse events was 25.2% with roflumilast vs 23.5% with vehicle in trial 1 and 25.9% with roflumilast vs 18.4% with vehicle in trial 2. The incidence of serious adverse events was 0.7% with roflumilast vs 0.7% with vehicle in trial 1 and 0% with roflumilast vs 0.7% with vehicle in trial 2.

Conclusions and Relevance  Among patients with chronic plaque psoriasis, treatment with roflumilast cream, 0.3%, compared with vehicle cream resulted in better clinical status at 8 weeks. Further research is needed to assess efficacy compared with other active treatments and to assess longer-term efficacy and safety.

Trial Registration  ClinicalTrials.gov Identifiers: NCT04211363, NCT04211389

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