Effect of Macitentan on the Development of New Ischemic Digital Ulcers in Patients With Systemic Sclerosis DUAL-1 and DUAL-2 Randomized Clinical Trials
Abstract
IMPORTANCE Digital ulcers in patients with systemic sclerosis are associated with pain and poor quality of life. Endothelin-1 promotes vasculopathy in systemic sclerosis after macitentan, an endothelin-1 blocker.
OBJECTIVE To evaluate the efficacy of macitentan in reducing the number of new digital ulcers in patients with systemic sclerosis. DESIGN, SETTING, AND PARTICIPANTS Two international, randomized, double-blind, placebo-controlled trials (DUAL-1, DUAL-2) were conducted between January 2012 and February 2014.
Participants were patients with systemic sclerosis and active digital ulcers at baseline. Target enrollment for each study was 285 patients.
INTERVENTIONS Patients were randomized (1:1:1) to receive oral doses of 3mg of macitentan, 10mg of macitentan, or placebo once daily and stratified according to number of digital ulcers at baseline (3 or >3). MAIN OUTCOMES AND MEASURES The primary outcome for each trialwas the cumulative number of new digital ulcers from baseline to week 16.
Treatment effect was expressed as the ratio between treatment groups.