POS1362 THE EFFICACY AND CYTOKINE PROFILES DURING TREATMENT WITH APREMILAST IN PATIENTS WITH BEHÇET ‘S DISEASE

Abstract

BackgroundApremilast has been shown to be effective in patients with Behçet’s disease (BD) in domains other than oral ulcers; however, its long-term efficacy is yet to be determined. Although serum cytokine modulation by increasing intracellular cAMP levels has been suggested as a mechanism for the efficacy of apremilast on skin areas of psoriasis [1], the relationship between efficacy and cytokine on various domains in BD has not been fully investigated.ObjectivesThis study aims to evaluate the long-term clinical efficacy of apremilast in BD and its effect on serum cytokines.MethodsIn this study, patients with BD who received apremilast for active oral ulcers were included. For 12 months, the improvement rates of oral and genital ulcers, skin lesions, and arthritis were assessed every three months. Serum levels of cytokines, including interferon-gamma (IFN-γ), interleukin 10 (IL-10), and IL-17A were determined using Simple Plex (Protein Simple, CA, USA) at baseline and three months after apremilast treatment. Other cytokines, including tumor necrosis factor-alpha (TNF-a), IL-6, IL-8, and IL-23, were also measured in serum using a multiplex immunoassay (Luminex Assay, R&D Systems).ResultsFifteen patients were included in this study. Table 1 shows the characteristics of the patients who participated in this study. Oral ulcers disappeared in 66.7% and 92.3% of the patients after 3 and 6 months of apremilast treatment, respectively. Genital ulcers disappeared in all patients after 6 months of apremilast treatment and were maintained for 12 months. The efficacy of apremilast in oral ulcers could be divided between two groups: 8 patients in the oral ulcer remission group (OU-R group) whose oral ulcers completely disappeared after 3 months of apremilast administration and persisted for 1 year, and 7 patients in the oral ulcer non-remission group (OU-NR group) whose oral ulcers persisted after 3 months of apremilast treatment. Genital ulcers improved more rapidly in the OU-R group than in the OU-NR group, and completely disappeared within 3 months. Skin and joint lesions generally improved after 6 months, but recurred after 9 months.Table 1.Baseline characteristics of the studied patients with Behçet’s diseaseCharacteristicsN = 15Age (years), mean ± SD46.7 ± 13.0Sex (female), n (%)11 (73.3)Disease duration (years), mean ± SD10.4 ± 8.8Active Behçet’s disease manifestation at the time of enrollment, n (%) Oral ulcer15 (100) Genital ulcer5 (33.3) Skin lesion (erythema nodosum or pustules)10 (66.7) Arthralgia9 (60.0) Arthritis5 (33.3) Ocular involvement0 (0) Gastrointestinal involvement1 (6.7) Neurological involvement0 (0) Vascular involvement0 (0)SD, standard deviation; n, number.Serum cytokines could be analyzed in seven of the 15 cases. There was no significant association between serum baseline cytokine levels and the presence of lesions or severity of disease. Compared to baseline, TNF-α and IL-23 levels were significantly lower after apremilast treatment and IFN-γ levels were trending upwards; however, IL-6, IL-8, and IL-10 levels showed no constant trend (TNF-α and IL-23: p <0.05, IFN-γ: p = 0.078). In addition, the rate of decrease in serum IL-6, IL-10, and IL-23 levels was significantly greater in the OU-R group than in the OU-NR group (Figure 1). However, the rate of change in serum cytokines was not associated with efficacy of apremilast for skin lesions, arthralgia, or arthritis.Figure 1.The rate of change in serum interleukin (IL)-6, IL-10, and IL-23 levels up to 3 months after apremilast treatment in the oral ulcer remission group and the oral ulcer non-remission group.ConclusionApremilast has shown long-term efficacy in the treatment of oral and genital ulcers in patients with BD. The efficacy of apremilast against oral ulcers in BD may be attributed to its modulatory effect on serum cytokines as previously reported. Future exploratory studies for biomarkers associated with the presence of efficacy against genital ulcer and arthritis are needed.