AB0669 THE EFFECTS OF BOSENTAN FOR TREATMENT OF DIGITAL ULCER IN KOREAN PATIENTS WITH SYSTEMIC SCLEROSIS: PROSPECTIVE, MULTICENTER, OPEN-LABEL TRIAL

Abstract

Background: Bosentan is an orally administered dual endothelin-1 (ET-1) receptor antagonist approved in the EU for reducing the number of new digital ulcers in patients with systemic sclerosis (SSc) and ongoing digital ulcer (DU). Oral bosentan therapy was beneficial and generally well tolerated in patients with DU associated with SSc. A total of 3 RCTs were identified. The first two were high quality (RAPIDS-1 and RAPIDS-2) with 122 and 188 patients and treatment durations of 16 and 24 weeks, respectively. Both studies showed that, compared with placebo, bosentan significantly reduced the number of new ulcers; however, it did not have an effect on the healing of preexisting ulcers and pain. Objectives: This study evaluated the efficacy and safety of bosentan in DU secondary to SSc in Korean patients. Methods: From December 2013 to Decemver 2017, a prospective, multicenter, open-label trial was performed to investigate the complete healing of DU and tolerability of bosentan in Korean patients with SSc. The SSc patients were included as having active DU or pulmonary arterial hypertension who had active DU in the last 3 months. A DU was defined as an area with visually discernable depth and a loss of continuity of epithelial coverage, which could be denuded or covered by a scab or necrotic tissue. If the area was denuded, the ulcer was designated active. If denudation could not be judged because of the presence of overlying scab or necrotic tissue, ulcers presenting with features, including underlying pain, based on investigator clinical judgment to be consistent with loss of epithelialization, epidermis, or dermis, and requiring treatment, were designated as active. The effectiveness and tolerability of bosentan was monitored within 24 weeks of study treatment, while healing of DU, largest diameter and the new incidence were also assessed up to week 24. Results: The primary objective of this study was to assess the efficacy of bosentan in reducing DU including the complete healing rate. Secondary endpoints included development of new DU, assessment of discontinuation, measures of nailfold capillaroscopic (NFC) change. Thirty-five SSc patients were enrolled and seventeen patients were included in the NFC analysis. Mean age was 50.5 year-old, 85.7% was woman, 68.6% were diffuse type of SSc, mean mRSS was 15.4 and mean disease duration was 77.9 months. Among 35 patients, 20 patients was finished 24 weeks treatment duration. The main reason for discontinuation is when the patient wants to stop because of the full effect of the drug (n=12, 80%). The side effects of the drug occurred in 4 cases during the treatment period. The mean number of DUs before treatment was 2.4 and was statistically decreased to 1.2 (p=0.001). From the 4th week of bosentan treatment, improvement of DU number was observed in 65.7% and complete healing was observed in 55% at 24 weeks. However, the mean size of largest DU diameter, remained at the end of treatment, was slightly increased from 4.1 to 5.2 mm, with no statistical significance. There was no statistically significant difference in the semi-quantitative changes of NFC before and after bosentan treatment. Conclusion: Administration of bosentan over 24 weeks was statistically associated with complete healing and significant reduction in net number of DU in Korean patients with SSc. However, the size of the remaining DU, that did not respond to bosentan, has rather increased. Disclosure of interests: None declared