title: RISE-SSc: Riociguat in diffuse cutaneous systemic sclerosis.
abstract: RISE-SSc is a randomized, double-blind, placebo-controlled phase 2 study investigating the efficacy and safety of riociguat in patients with diffuse cutaneous systemic sclerosis (dcSSc). Based on positive results from riociguat trials in patients with pulmonary hypertension and chronic thromboembolic pulmonary hypertension in combination with the known antiproliferative and antifibrotic effects seen in animal models, patients with SSc may benefit from treatment with riociguat. Patients with SSc meeting the ACR/EULAR systemic sclerosis classification criteria with diffuse cutaneous SSc (dcSSc) subset per LeRoy criteria, and a disease duration of less than or equal to 18 months will be randomized to placebo or riociguat 0.5 mg (up-titrated to a maximum dose of 2.5 mg TID over 10 weeks) and maintained on therapy for a total of 52 weeks. During the first 10 weeks of the long-term extension phase, placebo subjects will be up-titrated on riociguat, and all patients will be followed for up to 6 years. The primary endpoint of change in modified Rodnan skin score (mRSS) from baseline will be assessed at 52 weeks, as will be secondary endpoints such as mRSS progression and regression rates, patient quality of life, digital ulcer burden, and change in forced vital capacity and carbon monoxide diffusing capacity. This review will further define the clinical rationale for the use of riociguat in the treatment of SSc and provide details on study protocol, design, and outcome reporting.
  
  
  
  Clinicaltrials.gov identifier: NCT02283762.
authors.affiliation: Division of Rheumatology, University Hospital, Zurich, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
authors.affiliation: University of Western Ontario, London, ON, Canada.
authors.forename: Janet
authors.initials: J
authors.lastname: Pope
authors.affiliation: University College London, London, England, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Denton
authors.affiliation: Immunogenetics Cochin Institute, Paris, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
authors.affiliation: Division of Medicine & Rheumatology, University of Florence, Florence, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.affiliation: Bayer HealthCare, Whippany, NJ, USA.
authors.forename: Janethe
authors.initials: J
authors.lastname: de Oliveira Pena
authors.affiliation: Scleroderma Program, University of Michigan, Ann Arbor, MI, USA. Electronic address: khannad@med.umich.edu.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
mesh_terms: D002248:Carbon Monoxide / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D020536:Enzyme Activators / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D008297:Male; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D011655:Pulmonary Embolism / Q000188:drug therapy; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D011788:Quality of Life; D045743:Scleroderma, Diffuse / Q000188:drug therapy*; D012595:Scleroderma, Systemic / Q000145:classification; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012871:Skin Diseases / Q000188:drug therapy*; D000071756:Soluble Guanylyl Cyclase; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D020536:Enzyme Activators; D011720:Pyrazoles; D011743:Pyrimidines; D002248:Carbon Monoxide; D000071756:Soluble Guanylyl Cyclase; C542595:riociguat
keywords: Fibrosis; Riociguat; Soluble guanylate cyclase; Systemic sclerosis