Apremilast Reduces Oral Ulcers in Behçet Syndrome

Hatemi G, Melikoglu M, Tunc R, et al. Apremilast for Behçet’s Syndrome - A Phase 2, Placebo-Controlled StudyN Engl J Med 2015;372:1510-1518. doi: 10.1056/NEJMoa140868

Apremilast reduced the number of oral ulcers in Behçet’s syndrome in a Phase 2 study.

The trial randomized 111 patients to apremilast or placebo for 12 weeks, then switched the placebo group to apremilast for 12 weeks. Both groups were observed during a 4-week follow-on phase.

The primary end point was the number of oral ulcers at week 12. The mean number (± standard deviation) of oral ulcers at week 12 was 0.5 (±1.0) in the apremilast group vs 2.1 (±2.6) in the placebo group.

A secondary end point was pain from oral ulcers. On a 100-mm visual-analog scale, the mean reduction in pain was 45 mm with apremilast vs 16 mm with placebo.

Adverse effects of apremilast were similar to those found in previous studies of psoriasis and psoriatic arthritis: nausea, vomiting and diarrhea. There were two serious adverse events with apremilast: worsening of an anal fissure and hemorrhoids resulting from diarrhea  in one patient and transient paralysis of both legs in a second, which an investigator determined to be caused by conversion disorder.

Using indirect comparisons, the authors estimated that effect size for treatment of oral ulcers was greater than colchicine but less than etanercept.

Apremilast is a small oral inhibitor of phosphodiesterase-4, which modulates several inflammatory pathways.