BACKGROUND: The small-molecule phosphodiesterase 4 inhibitor apremilast 
modulates cytokines that are up-regulated in Behçet's syndrome. In a phase 2 
trial involving patients with Behçet's syndrome, apremilast reduced the 
incidence and severity of oral ulcers. Data on the efficacy and safety of 
apremilast in patients with Behçet's syndrome who had active oral ulcers and had 
not previously received biologic agents are limited.
METHODS: In a phase 3 trial, we randomly assigned, in a 1:1 ratio, patients who 
had Behçet's syndrome with active oral ulcers but no major organ involvement to 
receive either apremilast at a dose of 30 mg or placebo, administered orally, 
twice daily for 12 weeks, followed by a 52-week extension phase. The primary end 
point was the area under the curve (AUC) for the total number of oral ulcers 
during the 12-week placebo-controlled period (with lower values indicating fewer 
ulcers). There were 13 secondary end points, including complete response of oral 
ulcers, change from baseline in pain associated with oral ulcers, disease 
activity, and change from baseline in the Behçet's Disease Quality of Life score 
(range, 0 to 30, with higher scores indicating greater impairment in quality of 
life). Safety was also assessed.
RESULTS: A total of 207 patients underwent randomization (104 patients to the 
apremilast group and 103 to the placebo group). The AUC for the number of oral 
ulcers was 129.5 for apremilast, as compared with 222.1 for placebo 
(least-squares mean difference, -92.6; 95% confidence interval [CI], -130.6 to 
-54.6; P<0.001). The change from baseline in the Behçet's Disease Quality of 
Life score was -4.3 points in the apremilast group, as compared with -1.2 points 
in the placebo group (least-squares mean difference, -3.1 points; 95% CI, -4.9 
to -1.3). Adverse events with apremilast included diarrhea, nausea, and 
headache.
CONCLUSIONS: In patients with oral ulcers associated with Behçet's syndrome, 
apremilast resulted in a greater reduction in the number of oral ulcers than 
placebo but was associated with adverse events, including diarrhea, nausea, and 
headache. (Funded by Celgene; ClinicalTrials.gov number, NCT02307513.).