Treatment with apremilast 30 mg twice daily for 12 weeks led to a greater decrease in the number of oral ulcers and in associated pain for patients with Behçet syndrome than treatment with placebo, according to the results of a new phase III study. More than half of the patients treated with apremilast (53%) were free of oral ulcers at week 12, compared with 22% in the placebo group, and the benefits of the treatment were apparent as early as week 1.

Oral ulcers are an early and frequent manifestation of Behçet syndrome, and can have a substantial effect on a patient’s quality of life. Although a number of agents are available to treat oral ulcers, including colchicine, topical or systemic glucocorticoids, TNF inhibitors or thalidomide, some patients fail to respond to these treatments. Apremilast, an orally available small-molecule phosphodiesterase 4 (PDE4) inhibitor that is already approved for the treatment of psoriasis and psoriatic arthritis, is a potential treatment for Behçet syndrome as it modulates several pro-inflammatory mediators that are upregulated in the disease (TNF, IL-2, IL-8, IL-17 and IFNγ).

The phase III results are consistent with those of a previous phase II trial of patients with Behçet syndrome from Turkey and the USA, but the current trial included a larger group of patients (n = 207) from 10 countries across 3 continents. Also notable is that patients in the phase III study had failed to respond to previous treatment with one or more nonbiologic agents.

Compared with the placebo group, patients in the apremilast group had a greater improvement in Behçet’s Disease Quality of Life score, and in pain associated with oral ulcers as assessed on a 100-mm visual analogue scale. However, adverse events, including diarrhoea, nausea and headache, were more frequent in the apremilast group than the placebo group.

As the trial had no active comparator, further studies are needed to determine how the efficacy of apremilast compares with that of other agents. Longer follow-up is also required to determine whether long-term administration of apremilast could be safe and effective.