Apremilast Effective Treating Genital Ulcers Linked to Active Behcet's Syndrome

Gulen Hatemi, MD

Both oral ulcers (OU) and genital ulcers (GU) are major complications associated with Behcet’s syndrome.

In data planned for presentation during the European Congress of Rheumatology (EULAR) 2020 meeting, a team, led by Gulen Hatemi, MD, Istanbul University—Cerrahpaşa, Cerrahpaşa Medical School and Behçet’s Disease Research Center, tested the efficacy of apremilast (APR) for the treatment of genital ulcers linked to Behcet’s syndrome in the RELIEF study, as well as in a pooled data analysis of RELIEF and a phase 2 study.

Behcet’s syndrome, a chronic, multi-system inflammatory disorder, is characterized by painful, recurrent oral ulcers and genital ulcers, which can contribute to difficulties with sexual activity, walking, and sitting. The genital ulcers linked to Behcet’s syndrome could also cause scarring and could impair the quality of life.

The investigators tested apremilast, an oral phosphodiesterase 4 inhibitor that has demonstrated efficacy in the past in the treatment of the oral ulcers associated with Behcet's syndrome during a phase 3 randomized RELIEF study.

The study included 207 adult patients with active Behcet’s syndrome and ≥3 oral ulcers at randomization or ≥2 oral ulcers at screening and randomization, without active major organ involvement.

Each patient was randomized to either 30 mg of apremilast twice daily or placebo.

The investigators assessed clinical improvement in genital ulcers by evaluating the time to the first GU recurrence after loss of complete response, as well as the mean number of genital ulcers in patients without GU at baseline and the proportion of patients who were GU-free at week 12 regardless of baseline GU status.

In the pooled analysis of patients in RELIEF and a randomized phase 2 study, the investigators assessed achievement of GU complete response in patients with genital ulcers at baseline.

In patients with GU complete response before Week 12, the median time to the first GU recurrence after loss of complete response was based on Kaplan-Meier estimates and the mean number of GU was summarized descriptively using data as observed.

The between-group differences in the proportion of patients who were free of genital ulcers at week 12 were analyzed by Cochran-Mantel-Haenszel test using non-responder imputation to handle missing data.

Of the 207 participants in the study, 17 patients in the treatment group and 17 individuals in the placebo group had genital ulcers at baseline, with the mean GU counts of 2.9 and 2.6, respectively. Among the patients with GU at baseline in the RELIEF trial, 12 (70.6%) in the treatment group and 7 (41.2%) in the placebo group achieve GU complete response at week 12 (P = 0.110).

The median time to first GU recurrence in these patients occurred earlier in the placebo group (6.1 weeks) than it did in the apremilast group, which was not calculatable.

For the pooled analysis of both RELIEF and the phase 2 study, the investigators found a significantly greater proportion of patients with genital ulcers at baseline achieved a complete response at week 12 in the treatment group when compared to placebo (21/27 [77.8%] vs. 9/23 [39.1%]; P = 0.011).

On the other hand, the proportion of patients who were GU-free was significantly greater with apremilast (92/104 [88.5%]) compared to placebo (72/101 [71.3%]), regardless of baseline number of GU ( P = 0.002).

“The number of patients with GU was low, but the totality of the data shows a favorable trend in the treatment effect of APR on GU,” the authors wrote. “Greater proportions of APR-treated patients were GU-free at Week 12 vs. patients receiving [placebo], and the time to the first GU recurrence occurred earlier with [placebo] vs. APR.”

The study, “Efficacy Of Apremilast For The Treatment Of Genital Ulcers Associated With Active Behcet's Syndrome: A Combined Analysis Of Two Randomized Controlled Trials,” was published online by EULAR.