Mark G Lebwohl1, Kim A Papp1, Linda Stein Gold1, Melinda J Gooderham1, Leon H Kircik1, Zoe D Draelos1, Steven E Kempers1, Mathew Zirwas1, Kathleen Smith1, David W Osborne1, Marie-Louise Trotman1, Lynn Navale1, Charlotte Merritt1, David R Berk1, Howard Welgus1. 1. 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.
Abstract
BACKGROUND:Systemic 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. METHODS: In this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to useroflumilast 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. RESULTS: Among 331 patients who underwent randomization, 109 were assigned toroflumilast 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. CONCLUSIONS:Roflumilast 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.).
RCT Entities:
BACKGROUND: Systemic 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. METHODS: In 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. RESULTS: Among 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. CONCLUSIONS:Roflumilast 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.).
Authors: Mark G Lebwohl; Leon H Kircik; Angela Y Moore; Linda Stein Gold; Zoe D Draelos; Melinda J Gooderham; Kim A Papp; Jerry Bagel; Neal Bhatia; James Q Del Rosso; Laura K Ferris; Lawrence J Green; Adelaide A Hebert; Terry Jones; Steven E Kempers; David M Pariser; Paul S Yamauchi; Matthew Zirwas; Lorne Albrecht; Alim R Devani; Mark Lomaga; Amy Feng; Scott Snyder; Patrick Burnett; Robert C Higham; David R Berk Journal: JAMA Date: 2022-09-20 Impact factor: 157.335
Authors: Julie J Hong; Megan L Mosca; Edward K Hadeler; Nicholas D Brownstone; Tina Bhutani; Wilson J Liao Journal: Dermatol Ther (Heidelb) Date: 2021-04-29