BACKGROUND: The phase 2b Riociguat Safety and Efficacy in Patients with Diffuse Cutaneous Systemic Sclerosis (RISE-SSc) trial investigated riociguat versus placebo in early diffuse cutaneous systemic sclerosis. The long-term extension evaluated safety and exploratory treatment effects for an additional year. METHODS: Patients were enrolled to RISE-SSc between Jan 15, 2015, and Dec 8, 2016. Those who completed the 52-week, randomised, parallel-group, placebo-controlled, double-blind phase were eligible for the long-term extension. Patients originally assigned to riociguat continued therapy (riociguat-riociguat group). Those originally assigned to placebo were switched to riociguat (placebo-riociguat group), adjusted up to 2·5 mg three times daily in a 10-week, double-blind dose-adjustment phase, followed by an open-label phase. Statistical analyses were descriptive. Safety including adverse events and serious adverse events was assessed in the long-term safety analysis set (all patients randomly assigned and treated with study medication in the double-blind phase who continued study medication in the long-term extension). The RISE-SSc trial is registered with ClinicalTrials.gov, NCT02283762. FINDINGS: In total, 87 (72%) of 121 patients in the main RISE-SSc study entered the long-term extension (riociguat-riociguat, n=42; placebo-riociguat, n=45). 65 (75%) of 87 patients were women, 22 (25%) were men, and 62 (71%) were White. Overall, 82 (94%) of 87 patients in the long-term extension had an adverse event; most (66 [76%] of 87) were of mild to moderate severity, with no increase in pulmonary-related serious adverse events in patients with interstitial lung disease. INTERPRETATION: No new safety signals were observed with long-term riociguat in patients with early diffuse cutaneous systemic sclerosis. Study limitations include the absence of a comparator group in this open-label extension study. FUNDING: Bayer and Merck Sharp & Dohme.

Clinical Research Innovation and Education Center Tohuko University Sendai Japan

Department of Allergy and Rheumatology Nippon Medical School Tokyo Japan

Department of Clinical Internal Anesthesiological and Cardiovascular Sciences Sapienza University of Rome Rome Italy

Department of Experimental and Clinical Medicine University of Florence Florence Italy; Unit of Immunology Rheumatology Allergy and Rare Diseases IRCCS San Raffaele Hospital Milan Italy

Department of Internal Medicine and Clinical Immunology Referral Centre for Rare Systemic Autoimmune Diseases North and North West of France Centre Hospitalier Universitaire Lille University of Lille Inserm U1286 INFINITE Institute for Translational Research in Inflammation Lille France

Department of Rheumatology and Immunology Medical School University of Pécs Pécs Hungary

Department of Rheumatology CHU Bordeaux University Hospital Bordeaux France

Department of Rheumatology Endocrinology and Nephrology Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan

Department of Rheumatology Ghent University Hospital Ghent Belgium; Department of Internal Medicine Ghent University Hospital Ghent Belgium; Unit for Molecular Immunology and Inflammation VIB Inflammation Research Center Ghent Belgium

Department of Rheumatology St Vincent's Hospital Melbourne VIC Australia

Department of Rheumatology University Hospital Zurich University of Zurich Zurich Switzerland

Department of Rheumatology University of Debrecen Debrecen Hungary

Division of Medicine Centre for Rheumatology UCL London UK

Division of Rheumatology and Immunology Medical University of South Carolina Charleston SC USA

Division of Rheumatology Department of Internal Medicine Michigan Medicine University Hospital Ann Arbor MI USA; University of Michigan Scleroderma Program Ann Arbor MI USA

Division of Rheumatology Georgetown University Washington DC USA

Institute of Rheumatology Department of Rheumatology 1st Faculty of Medicine Charles University Prague Czech Republic

Ishii Hospital Division of Dermatology Isezaki Gunma Japan

Laboratory of Tissue Homeostasis and Disease Skeletal Biology and Engineering Research Center Department of Development and Regeneration KU Leuven Division of Rheumatology University Hospitals Leuven Belgium

Medical College of Georgia at Augusta University Augusta GA USA

Research and Development Bayer Wuppertal Germany

Rheumatology A Department Cochin Hospital APHP Paris Descartes University Paris France

Rheumatology Unit Department of Clinical and Experimental Medicine University of Pisa Pisa Italy

Schulich School of Medicine Division of Rheumatology University of Western Ontario London ON Canada

StatFinn Espoo Finland; Bayer Espoo Finland

Toronto Scleroderma Program Division of Rheumatology Department of Medicine Toronto Western Hospital University Health Network Mount Sinai Hospital and University of Toronto Toronto ON Canada

References provided by Crossref.org

Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis

See more in PubMed

ClinicalTrials.gov
NCT02283762