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.).