• Mark G Lebwohl, Kim A Papp, Linda Stein Gold, Melinda J Gooderham, Leon H Kircik, Zoe D Draelos, Steven E Kempers, Mathew Zirwas, Kathleen Smith, David W Osborne, Marie-Louise Trotman, Lynn Navale, Charlotte Merritt, David R Berk, Howard Welgus, and ARQ-151 201 Study Investigators.
• From the Icahn School of Medicine at Mount Sinai, New York (M.G.L., L.H.K.); Probity Medical Research and K. Papp Clinical Research, Waterloo (K.A.P.), and the SkiN Centre for Dermatology, Probity Medical Research and Queen's University, Peterborough (M.J.G.) - both in Ontario, Canada; Henry Ford Medical Center, Detroit (L.S.G.); Indiana Medical Center, Indianapolis (L.H.K.); Physicians Skin Care and DermResearch, Louisville, KY (L.H.K.); Dermatology Consulting Services, High Point, NC (Z.D.D.); Minnesota Clinical Study Center, Fridley (S.E.K.); Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley (M.Z.); and Arcutis Biotherapeutics, Westlake Village (K.S., D.W.O., L.N., C.M., D.R.B., H.W.), and ML Trotman Consulting, Newbury Park (M.-L.T.) - both in California.
• N. Engl. J. Med. 2020 Jul 16; 383 (3): 229-239.

BackgroundSystemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis.MethodsIn this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to use roflumilast 0.3% cream, roflumilast 0.15% cream, or vehicle (placebo) cream once daily for 12 weeks. The primary efficacy outcome was the investigator's global assessment (IGA) of a status of clear or almost clear at week 6 (assessed on a 5-point scale of plaque thickening, scaling, and erythema; a score of 0 indicates clear, 1 almost clear, and 4 severe). Secondary outcomes included an IGA score indicating clear or almost clear plus a 2-grade improvement in the IGA score for the intertriginous area and the change in the Psoriasis Area and Severity Index (PASI) score (range, 0 to 72, with higher scores indicating worse disease). Safety was also assessed.ResultsAmong 331 patients who underwent randomization, 109 were assigned to roflumilast 0.3% cream, 113 to roflumilast 0.15% cream, and 109 to vehicle cream. An IGA score indicating clear or almost clear at week 6 was observed in 28% of the patients in the roflumilast 0.3% group, in 23% in the roflumilast 0.15% group, and in 8% in the vehicle group (P<0.001 and P = 0.004 vs. vehicle for roflumilast 0.3% and 0.15%, respectively). Among the approximately 15% of patients overall who had baseline intertriginous psoriasis of at least mild severity, an IGA score at week 6 indicating clear or almost clear plus a 2-grade improvement in the intertriginous-area IGA score occurred in 73% of the patients in the roflumilast 0.3% group, 44% of those in the roflumilast 0.15% group, and 29% of those in the vehicle group. The mean baseline PASI scores were 7.7 in the roflumilast 0.3% group, 8.0 in the roflumilast 0.15% group, and 7.6 in the vehicle group; the mean change from baseline at week 6 was -50.0%, -49.0%, and -17.8%, respectively. Application-site reactions occurred with similar frequency in the roflumilast groups and the vehicle group.ConclusionsRoflumilast cream administered once daily to affected areas of psoriasis was superior to vehicle cream in leading to a state of clear or almost clear at 6 weeks. Longer and larger trials are needed to determine the durability and safety of roflumilast in psoriasis. (Funded by Arcutis Biotherapeutics; ARQ-151 201 ClinicalTrials.gov number, NCT03638258.).Copyright © 2020 Massachusetts Medical Society.

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