ISTANBUL, TURKEY – The investigational oral phosphodiesterase-4 inhibitor apremilast showed dramatic efficacy in the treatment of oral and genital ulcers of Behçet’s syndrome in a randomized, double-blind clinical trial.
The multicenter phase II study included 111 Behçet’s syndrome patients with active oral ulcers. They were randomized to 12 weeks of double-blind apremilast at 30 mg twice daily or placebo followed by an additional 12 weeks of open-label apremilast for all, then 4 weeks of post-treatment observation.
Participants had a mean of 2.8 oral ulcers at baseline. The primary study endpoint was the number present at week 12: a mean of 0.5 in the apremilast group, compared with 2.1 in controls, Dr. Gülen Hatemi reported at the annual congress of the European Academy of Dermatology and Venereology.
A total of 71% of patients in the apremilast group were oral ulcer–free at week 12, as were 29% of controls, added Dr. Hatemi, a rheumatologist at Istanbul (Turkey) University.
The benefit of apremilast occurred rapidly. The full response was seen at week 2 and was then maintained throughout the remainder of the 12 weeks of double-blind therapy and the following 12 weeks of open-label apremilast. However, oral ulcers returned in full force quickly after treatment cessation.
Pain from oral ulcers on a 0-100 visual analog scale plummeted in the apremilast group by a mean 44.7 points from a baseline of score of 54. In contrast, pain scores in the control group improved by 16 points, which is less than the 20-point threshold accepted as being clinically meaningful.
Behçet’s syndrome is an immune-mediated small-vessel vasculitis. Its mucocutaneous manifestations can be disabling and resistant to conventional therapies, Dr. Hatemi noted.
Only 16 patients had genital ulcers. All 10 randomized to apremilast were free of the ulcers at week 12, as were three of six affected patients in the control group.
Average scores on the Behçet’s Disease Activity Index dropped from 3.4 at baseline to 2.0 at 12 weeks in the apremilast arm while remaining unchanged in controls. Mean scores on the Behçet’s Disease Quality of Life instrument decreased by 4.5 points from a baseline of 12.6 in apremilast-treated patients, compared with a 1.6-point reduction in controls.
The investigators said no serious adverse events were related to apremilast.
Dr. Hatemi received a research grant from Celgene, the study sponsor, which is also developing the oral drug as a possible treatment for psoriasis, psoriatic arthritis, and ankylosing spondylitis.