Trial of Apremilast for Oral Ulcers in Behcet's Syndrome

BackgroundThe small-molecule phosphodiesterase 4 inhibitor apremilast modulates cytokines that are up-regulated in Behcet's syndrome. In a phase 2 trial involving patients with Behcet's syndrome, apremilast reduced the incidence and severity of oral ulcers. Data on the efficacy and safety of apremilast in patients with Behcet's syndrome who had active oral ulcers and had not previously received biologic agents are limited. MethodsIn a phase 3 trial, we randomly assigned, in a 1:1 ratio, patients who had Behcet'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 Behcet's Disease Quality of Life score (range, 0 to 30, with higher scores indicating greater impairment in quality of life). Safety was also assessed. ResultsA 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 Behcet'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. ConclusionsIn patients with oral ulcers associated with Behcet'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.) In a phase 3 trial involving patients with Behcet's syndrome, the small-molecule phosphodiesterase 4 inhibitor apremilast reduced the number of oral ulcers and pain of ulcers and improved quality-of-life measures as compared with placebo over 12 weeks. Adverse events included diarrhea, nausea, and headache.