Apremilast for Behçet’s Syndrome — A Phase 2, Placebo-Controlled Study

Estándar

Gulen Hatemi, M.D., Melike Melikoglu, M.D., Recep Tunc, M.D., Cengiz Korkmaz, M.D., Banu Turgut Ozturk, M.D., Cem Mat, M.D., Peter A. Merkel, M.D., Kenneth T. Calamia, M.D., Ziqi Liu, Ph.D., Lilia Pineda, M.D., Randall M. Stevens, M.D., Hasan Yazici, M.D., and Yusuf Yazici, M.D.. N Engl J Med 2015; 372:1510-1518April 16, 2015DOI: 10.1056/NEJMoa1408684

Abstract

BACKGROUND

Oral ulcers, the hallmark of Behçet’s syndrome, can be resistant to conventional treatment; therefore, alternative agents are needed. Apremilast is an oral phosphodiesterase-4 inhibitor that modulates several inflammatory pathways.

METHODS

We conducted a phase 2, multicenter, placebo-controlled study in which 111 patients with Behçet’s syndrome who had two or more oral ulcers were randomly assigned to receive 30 mg of apremilast twice daily or placebo for 12 weeks. This regimen was followed by a 12-week extension phase in which the placebo group was switched to apremilast and a 28-day post-treatment observational follow-up phase. The patients and clinicians were unaware of the study assignments throughout the trial. The primary end point was the number of oral ulcers at week 12. Secondary outcomes included pain from these ulcers (measured on a 100-mm visual-analogue scale, with higher scores indicating worse pain), the number of genital ulcers, overall disease activity, and quality of life.

RESULTS

The mean (±SD) number of oral ulcers per patient at week 12 was significantly lower in the apremilast group than in the placebo group (0.5±1.0 vs. 2.1±2.6) (P<0.001). The mean decline in pain from oral ulcers from baseline to week 12 was greater with apremilast than with placebo (−44.7±24.3 mm vs. −16.0±32.5 mm) (P<0.001). Nausea, vomiting, and diarrhea were more common in the apremilast group (with 22, 9, and 12 incidents, respectively, among 55 patients) than in the placebo group (with 10, 1, and 2 incidents, respectively, among 56 patients), findings that were similar to those in previous studies of apremilast. There were two serious adverse events in patients receiving apremilast.

CONCLUSIONS

Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçet’s syndrome. This preliminary study 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. (Funded by Celgene; ClinicalTrials.gov number, NCT00866359.)