BACKGROUND: Oral ulcers, the hallmark of Behçet's syndrome, can be resistant to 
conventional treatment; therefore, alternative agents are needed. Apremilast is 
an oral phosphodiesterase-4 inhibitor that modulates several inflammatory 
pathways.
METHODS: We conducted a phase 2, multicenter, placebo-controlled study in which 
111 patients with Behçet's syndrome who had two or more oral ulcers were 
randomly assigned to receive 30 mg of apremilast twice daily or placebo for 12 
weeks. This regimen was followed by a 12-week extension phase in which the 
placebo group was switched to apremilast and a 28-day post-treatment 
observational follow-up phase. The patients and clinicians were unaware of the 
study assignments throughout the trial. The primary end point was the number of 
oral ulcers at week 12. Secondary outcomes included pain from these ulcers 
(measured on a 100-mm visual-analogue scale, with higher scores indicating worse 
pain), the number of genital ulcers, overall disease activity, and quality of 
life.
RESULTS: The mean (±SD) number of oral ulcers per patient at week 12 was 
significantly lower in the apremilast group than in the placebo group (0.5±1.0 
vs. 2.1±2.6) (P<0.001). The mean decline in pain from oral ulcers from baseline 
to week 12 was greater with apremilast than with placebo (-44.7±24.3 mm vs. 
-16.0±32.5 mm) (P<0.001). Nausea, vomiting, and diarrhea were more common in the 
apremilast group (with 22, 9, and 12 incidents, respectively, among 55 patients) 
than in the placebo group (with 10, 1, and 2 incidents, respectively, among 56 
patients), findings that were similar to those in previous studies of 
apremilast. There were two serious adverse events in patients receiving 
apremilast.
CONCLUSIONS: Apremilast was effective in treating oral ulcers, which are the 
cardinal manifestation of Behçet's syndrome. This preliminary study was neither 
large enough nor long enough to assess long-term efficacy, the effect on other 
manifestations of Behçet's syndrome, or the risk of uncommon serious adverse 
events. (Funded by Celgene; ClinicalTrials.gov number, NCT00866359.).