BACKGROUND: Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune 
responses associated with psoriasis.
OBJECTIVES: ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice 
daily for moderate-to-severe plaque psoriasis.
METHODS: This phase III, double-blind, placebo-controlled trial randomized 
adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched 
to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in 
Psoriasis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to 
continue apremilast or receive placebo. Upon loss of 50% of PASI improvement 
obtained at week 32, patients rerandomized to placebo resumed apremilast.
RESULTS: The modified intention-to-treat population (full analysis set) included 
137 placebo and 274 apremilast patients. At week 16, significantly more 
apremilast patients achieved PASI 75 (28·8%), PASI 50 (55·5%) and static 
Physician's Global Assessment score of 0 or 1 (20·4%) vs. placebo (5·8%, 19·7%, 
4·4%, respectively; P < 0·001). Most patients rerandomized to apremilast at week 
32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast 
showed significant improvements in quality of life (as assessed by the 
Dermatology Life Quality Index) and pruritus at week 16 compared with placebo 
(P < 0·001). The exposure-adjusted incidence of adverse events did not increase 
with continued apremilast treatment for up to 52 weeks. The most common adverse 
events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract 
infection.
CONCLUSIONS: Apremilast was effective in the treatment of moderate-to-severe 
plaque psoriasis over 52 weeks.