Background/Purpose: Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated efficacy in a global, phase III, multicenter, randomized, double-blind, placebo-controlled study in patients with Behçet’s syndrome and active oral ulcers previously treated with ≥1 non-biologic therapy. A subgroup analysis was performed for Japanese patients in this study. We assessed the efficacy and safety of apremilast compared with placebo over 12 weeks in the subgroup of Japanese patients with Behçet’s syndrome in the study.

Methods: In the global study, 207 patients with Behçet’s syndrome were randomized (1:1) to apremilast 30 mg BID (n=104) or placebo (n=103) for 12 weeks, followed by a 52-week active-treatment phase. Patients were stratified by region (Japan and “Other”). Patients had active Behçet’s syndrome, with ≥3 oral ulcers at randomization or ≥2 oral ulcers at screening and randomization without major organ involvement. The primary endpoint was the area under the curve (AUC_Wk0-12) for the total number of oral ulcers over 12 weeks. Additional endpoints included the assessments of oral ulcers, including pain, overall disease activity (Behçet’s Syndrome Activity Score [BSAS] and Behçet’s Disease Current Activity Form [BDCAF]), and quality of life (QoL) at Week 12. The primary and secondary variables in the Japanese subset analysis were pre-specified without adjustment for multiplicity. Nominal P values are presented.

Results: A total of 39 patients were included in the Japanese subgroup (placebo: n=20; apremilast: n=19). The subgroup analysis showed that the AUC_Wk0-12 for oral ulcers was significantly lower in the apremilast group compared with the placebo group over 12 weeks (Table), which is consistent with the findings of the overall study population (129.5 vs. 222.1; P<0.0001). Similarly, as observed in the overall population, significantly greater improvements were shown in complete response rate of oral ulcers and maintenance of complete response of oral ulcers, time to oral ulcer resolution, and BSAS at Week 12 in the apremilast group. Numerical improvements were observed in oral ulcer pain, BDCAF, and QoL at Week 12 in the apremilast group; unlike the overall population, significance was not achieved, likely due to the limitation of the small sample size. Treatment-emergent adverse events (AEs) were comparable between the apremilast (73.7%) and placebo (75.0%) treatment groups. One serious AE (migraine) was reported with apremilast treatment. No AEs led to discontinuation.

Conclusion: The Japanese subgroup analysis showed that apremilast reduced the number of oral ulcers and overall disease activity and had favorable effects on oral ulcer pain and QoL in patients with Behçet’s syndrome and active oral ulcers over 12 weeks. The safety profile was consistent with the known safety profile of apremilast, and results were consistent with findings in the overall study population.