BACKGROUND: Oral phosphodiesterase (PDE)4 inhibitors have shown efficacy in 
chronic obstructive pulmonary disease and psoriasis.
OBJECTIVES: To assess the effectiveness, local safety and tolerability, and 
systemic pharmacokinetics of two topical PDE4 inhibitors, roflumilast and 
TAK-084, in plaque psoriasis.
METHODS: An intraindividual comparison of six topical products was made in 15 
patients aged 18-65 years with stable chronic plaque psoriasis in an 
investigator-blinded, within-subject randomized study. The products evaluated 
were calcipotriol 0·005% cream; betamethasone valerate 0·1% (both in their 
marketed formulations); investigational cream formulations of roflumilast 0·5% 
and TAK-084 0·5% and 5%; and a vehicle cream formulation as a control. Each 
treatment was applied daily to different test sites located on psoriasis plaques 
for 3 weeks.
RESULTS: The primary end point of (mean) change from baseline in skin infiltrate 
thickness after 3 weeks of treatment showed statistically significant 
improvements for all treatments: betamethasone valerate cream (-286·9 μm), the 
selective PDE4 inhibitors roflumilast 0·5% (-237·1 μm) and TAK-084 (0·5% cream, 
-153·6 μm; 5% cream, -216·7 μm) and calcipotriol 0·005% (-187·7 μm) when 
compared with vehicle cream control (all P < 0·001). Both the TAK-084 5% and 
roflumilast 0·5% formulations performed well overall compared with the potent 
corticosteroid, betamethasone, and were ranked better than the vitamin D 
analogue calcipotriol. All adverse events were mild or moderate and none was 
serious.
CONCLUSIONS: Topical treatment with cream formulations of the PDE4 inhibitors 
roflumilast and TAK-084 reduced inflammation, measured as a change in skin 
infiltrate thickness, and reduced psoriasis severity. Corticosteroid treatments 
have known systemic and cutaneous side-effects; PDE4 inhibitors could offer an 
alternative to these and deserve further study.