FRI0231 TREATMENT OF DIGITAL ULCERS IN PATIENTS WITH SYSTEMIC SCLEROSIS: PROSPECTIVE COHORT STUDY

Abstract

Background:Digital ulcer (DU) is a common clinical manifestation in patients with systemic sclerosis (SSc). About 70% of patients with SSc experience DUs during the first 10 years, which limit daily activities and may result in digital gangrene or amputation. Several vasoactive/vasodilating agents have been suggested for treatment, but few studies have compared the efficacy of those drugs.Objectives:The objective of our study was to compare the efficacy of medical treatment for SSc related-DUs, focusing on on endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitors (PDE5inh).Methods:In this prospective observational cohort study, we recruited patients who had one or more active SSc-related DUs and newly started or changed a medical treatment for SSc-related DUs from 13 medical centers in South Korea. The primary outcome was to compare the time to resolution of cardinal DU (CU) according to the treatments. The secondary outcomes included changes in the size or number of CU and changes in the number of DUs. CU was defined as the most clinically significant DU chosen by the investigators. Patients were followed up at every 4 weeks after enrollment until 12 weeks and finally at 24 weeks.Results:Seventy-one patients were enrolled. Seven patients were excluded due to follow-up loss or withdrawal of consent. A total of 64 patients were analyzed. Seventy-eight percent (n=50) were female. The mean age at enrollment was 49.6 ± 11.6 year-old, and the mean disease duration was 7.1 ± 5.9 years. Twenty-eights pateitns (43.8%) were limited SSc. Forty-nine patients (n=76.6%) started ERA treatment (bosentan=49). Eleven patients (17.2%) started PDE5inh treatment (n=9 for sildenafil, n=1 for udenafil, and n=1 for tadalafil). Four patients who started medication other than ERA or PDE5inh classified as other treatment groups. Seventeen patients (26.6%) were on background calcium channel blockers (CCBs). CU healed in 25 patients (39.1%) at 12 weeks and 43 patients (67.2%) at 24 weeks. The mean time to heal CUs were 54.4 ± 22.7 days at 12 weeks and 91.6 ± 49.2 days at 24 weeks. Time to heal CU was comparable among patients on ERA, PDE5inh, and others (p=0.53, figure 1). The CU area was comparable among the three groups at baseline, 12, and 24 weeks. The mean area of CU in patients on ERA at baseline at 12, and 24 weeks was 21.3±19.4 mm2, 8.2±14.6 mm2, and 4.6±7.7 mm2, respectively. The mean area of CU in patients with PDE5inh at baseline at 12, and 24 weeks was 26.2±28.1 mm2, 3.5±3.6 mm2, and 1.3±4.3 mm2. New DUs developed in 4 patients (8.3%) in ERA, whereas 4 patients (40.0%) in PDE5inh at 4 weeks. The use of ERA was significantly associated with less new DUs development than the use of PDE5inh at 4 weeks follow-up (RR for developing new DU patients on ERA, 0.21; 95% CI 0.06-0.70; p=0.02) At 24 weeks follow-up, none of the patients on CCB developed new DUs.Conclusion:The time to heal CU for ERA and PDEinh users was comparable in the current study. ERA treatment was associated with reduced new DU occurrence compared with PDE5inh treatment. None of the patients with CCB treatment developed new DU development at 24 weeks.Acknowledgments:This study was supported by Handok Pharmaceutical Inc., Seoul, Republic of Korea.Disclosure of Interests:Sung Hae Chang: None declared, Jae-Bum Jun Grant/research support from: Clinical trials; Corbus, JW Pharmaceutical, Speakers bureau: SK Chemical, Yun Jong Lee: None declared, Tae Young Kang: None declared, Yongbeom Park: None declared, Seung-Geun Lee: None declared, Shin-Seok Lee: None declared, Eun Bong Lee: None declaredFigure 1