Apremilast heals oral ulcers in Behçet’s syndrome

Key clinical point: The oral anti-inflammatory agent apremilast reduced the number of oral ulcers in a preliminary study of Behçet’s syndrome.

Major finding: The primary efficacy endpoint – the mean number of oral ulcers at week 12 – was significantly lower in the apremilast group (0.5) than in the placebo group (2.1).

Data source: A phase II randomized placebo-controlled trial involving 111 patients in Turkey and the United States treated for 12-24 weeks.

Disclosures: This study was funded by Celgene, which was also involved in data management, analysis, and interpretation. Dr. Hatemi reported receiving grant support and personal fees from Celgene, and her associates reported ties to Celgene, Bristol-Myers Squibb, GlaxoSmithKline, Alexion, Sanofi, and AbbVie.



Apremilast reduced the number and pain of oral ulcers in patients with Behçet’s syndrome in an industry-sponsored phase II trial, according to a report published online April 16 in the New England Journal of Medicine.

“Any new drug that is effective against oral ulcers (the hallmark lesion of Behçet’s syndrome) may be a candidate for the treatment of other aspects of the disease,” said Dr. Gulen Hatemi of Istanbul University Cerrahpasa, and her associates.

Behçet’s syndrome is characterized by inflammation of the small blood vessels and mucocutaneous lesions, including oral ulcers, genital ulcers, papulopustular lesions, and nodular lesions. These can be disabling and have a substantial negative impact on quality of life. Apremilast is an oral inhibitor of phosphodiesterase-4 that acts on several different inflammatory pathways, has recently been approved for use in psoriasis and psoriatic arthritis, and appears to be a promising treatment for other chronic inflammatory conditions.

The investigators assessed the agent’s efficacy against Behçet’s syndrome in a double-blind trial in which 111 adults at three university hospitals in Turkey and three in the United States were randomly assigned to receive oral apremilast or a matching placebo twice daily for 12 weeks. All the study participants then were given apremilast for a further 12 weeks, after which all were observed during a 4-week follow-up phase with no treatment.

All the study participants had at least two oral ulcers at baseline. The primary efficacy endpoint was the mean number of oral ulcers at week 12. This was significantly lower in the apremilast group (0.5) than in the placebo group (2.1). The median number of oral ulcers also was significantly different, at 0 (range, 0-6) for apremilast and 2 (range, 0-13) for placebo. Apremilast induced improvement within 2 weeks; that effect was sustained throughout the entire 24-week treatment phase of the study and reverted when the drug was discontinued, according to Dr. Hatemi and her associates (N. Engl. J. Med. 2015 April 16 [doi:10.1056/NEJMoa1408684]).

On a scale of 1-100, mean pain scores at baseline were 54.3 in the apremilast group and 51.2 in the placebo group. By week 12, these scores declined significantly with apremilast by 44.7 points, compared with only 16 points for placebo. At week 24, pain scores remained low in the patients who received apremilast throughout the study, and declined by a similar degree (–42.2 points) in those who switched from placebo to apremilast.

In addition, 10 patients in the apremilast group had genital ulcers at baseline, and all were free from genital ulcers at week 12. Several measures of disease activity and quality of life showed significant improvements with apremilast but not with placebo. Adverse events including nausea, diarrhea, vomiting, and fatigue occurred more frequently with apremilast than with placebo.

However, “this was a preliminary study that was neither large enough nor long enough to assess long-term efficacy, the effect on other manifestations of Behçet’s syndrome, or the risk of uncommon serious adverse events,” the investigators noted.

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