Background: Roflumilast cream (ARQ-151) is a highly potent, selective 
phosphodiesterase-4 inhibitor in development for once-daily topical treatment of 
chronic plaque psoriasis. Objectives: To assess the safety and efficacy of 
once-daily roflumilast cream 0.5% and 0.15% in patients with chronic plaque 
psoriasis. Methods: This phase 1/2a study enrolled a single-dose, open-label 
cohort (Cohort 1: 0.5% cream applied to 25 cm² psoriatic plaques), and a 28-day, 
double-blinded cohort (Cohort 2: 1:1:1 randomization to roflumilast cream 0.5%, 
0.15%, or vehicle). Patients had chronic plaque psoriasis of >6 months' duration 
with ≤5% body surface area involvement. Outcomes included safety (adverse 
events) and efficacy (percentage change in the Target Plaque Severity Score 
[TPSS] × Target Plaque Area [TPA]) at week 4. Results: For Cohorts 1 (n=8) and 2 
(n=89), adverse events (all mild/moderate; none severe or serious) were similar 
between active arms and vehicle. Treatment-related events were confined to the 
application site, without differences between drug and vehicle. No patient 
discontinued treatment due to adverse events. The primary efficacy endpoint was 
met for both roflumilast cream doses: TPSS×TPA improvement at week 4 was 
statistically significant for roflumilast 0.5% (P=0.0007) and 0.15% (P=0.0011) 
versus vehicle; significance was reached as early as 2 weeks. For both 
roflumilast cream doses, 66%-67% improvement from baseline was observed at week 
4, without reaching a plateau, versus 38% improvement for vehicle. Conclusion: 
Roflumilast cream was safe and highly effective at doses of 0.5% and 0.15% and 
represents a potential novel once-daily topical therapy for the treatment of 
chronic plaque psoriasis. ClinicalTrials.gov NCT03392168. J Drugs Dermatol. 
2020;19(8): doi:10.36849/JDD.2020.5370.