FRI0303 THE EFFECTS OF RIOCIGUAT ON RAYNAUD'S PHENOMENON AND DIGITAL ULCERS IN PATIENTS WITH DIFFUSE SYSTEMIC SCLEROSIS: RESULTS FROM THE PHASE IIB RISE-SSC STUDY

Abstract

Background/Purpose: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of pulmonary arterial hypertension associated with connective tissue disease. It was anticipated that riociguat might, through its vasodilatory and anti-remodeling properties, decrease the number and severity of Raynaud's attacks and reduce net digital ulcer burden in patients with diffuse cutaneous systemic sclerosis (dcSSc). We present exploratory endpoints from the RISE-SSc study (NCT02283762) on the effect of riociguat in early dcSSc patients with Raynaud's phenomenon and digital ulcers. Methods: RISE-SSc was a Phase IIb, multicenter, randomized, double-blind, placebo-controlled study. Inclusion criteria were: diagnosis of SSc fulfilling ACR/EULAR criteria, diffuse cutaneous involvement, disease duration ≤18 months, and modified Rodnan skin score ≥10 and ≤22 units. Patients were assigned to placebo or riociguat individually adjusted from 0.5 mg up to 2.5 mg 3 times daily. Exploratory efficacy endpoints included 1) change in Raynaud's attacks from baseline to Week 14, assessed by the following individual outcome measures: Raynaud's condition score (analyzed using ANOVA), patient/physician assessment of Raynaud's phenomenon (analyzed using ANOVA), attack symptoms, attack duration, and average No. of attacks per day; and 2) change in net digital ulcer burden from baseline to Week 52, assessed by ulcer count, ulcer burden, and visual analog score (as part of the Scleroderma Health Assessment Questionnaire) for patientreported severity. Endpoints were analyzed using mixed-model repeated measures from baseline up to Week 52, unless otherwise stated. Results: In total, 121 patients were enrolled. At Week 14, a numerically greater relative reduction in attack duration and attack frequency was observed from baseline in the riociguat group vs placebo (Table). Improvements in Raynaud's attack symptoms and disability measured by pain, numbness, tingling, and patient/physician global assessment were also observed with riociguat vs placebo (Table). At Week 52, reductions in net digital ulcer burden were -0.09±0.50 for riociguat and - 0.08±1.47 for placebo (estimated treatment difference: -0.11 [95% CI: -0.38, 0.17; p=0.44]). At baseline, 9 patients (15.0%) had digital ulcers in the riociguat arm vs 6 patients (9.8%) in the placebo arm. At Week 52, 1 patient (2.1%) had digital ulcers in the riociguat arm vs 4 patients (8.2%) in the placebo arm. Conclusion: There was a numerical tendency toward a reduction of Raynaud's phenomenon symptoms with riociguat treatment compared with placebo. While there was no significant difference in reduction of net digital ulcer burden between riociguat and placebo, data suggest that riociguat may prevent digital ulcer recurrence in patients with early dcSSc. (Table Presented).