OBJECTIVES: Riociguat is approved for pulmonary arterial hypertension and has antiproliferative, anti-inflammatory and antifibrotic effects in animal models of tissue fibrosis. We evaluated the efficacy and safety of riociguat in patients with early diffuse cutaneous systemic sclerosis (dcSSc) at high risk of skin fibrosis progression. METHODS: In this randomised, double-blind, placebo-controlled, phase IIb trial, adults with dcSSc of <18 months' duration and a modified Rodnan skin score (mRSS) 10-22 units received riociguat 0.5 mg to 2.5 mg orally three times daily (n=60) or placebo (n=61). The primary endpoint was change in mRSS from baseline to week 52. RESULTS: At week 52, change from baseline in mRSS units was -2.09±5.66 (n=57) with riociguat and -0.77±8.24 (n=52) with placebo (difference of least squares means -2.34 (95% CI -4.99 to 0.30; p=0.08)). In patients with interstitial lung disease, forced vital capacity declined by 2.7% with riociguat and 7.6% with placebo. At week 14, average Raynaud's condition score had improved ≥50% in 19 (41.3%)/46 patients with riociguat and 13 (26.0%)/50 patients with placebo. Safety assessments showed no new signals with riociguat and no treatment-related deaths. CONCLUSIONS: Riociguat did not significantly benefit mRSS versus placebo at the predefined p<0.05. Secondary and exploratory analyses showed potential efficacy signals that should be tested in further trials. Riociguat was well tolerated.

Bayer Healthcare Beijing China

Bayer HealthCare Pharmaceuticals Inc Whippany New Jersey USA

Clinical Research Innovation and Education Center Tohoku University Hospital Sendai Japan

Department of Allergy and Rheumatology Nippon Medical School Graduate School of Medicine Tokyo Japan

Department of Clinical Medicine and Therapy University of Rome La Sapienza Rome Italy

Department of Dermatology Gunma University Postgraduate School of Medicine Maebashi Japan

Department of Experimental and Clinical Medicine University of Florence Firenze Italy

Department of Internal Medicine and Clinical Immunology Claude Huriez Hospital Lille University School of Medicine Lille France

Department of Rheumatology and Immunology University of Pécs Pécs Hungary

Department of Rheumatology and Internal Medicine Ghent University Hospital Ghent Belgium

Department of Rheumatology CHU Bordeaux Bordeaux France

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

Department of Rheumatology St Vincent's Hospital Melbourne Melbourne Victoria Australia

Department of Rheumatology University Hospital Zurich Switzerland

Division of Medicine Centre for Rheumatology University College London London UK

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

Division of Rheumatology Department of Internal Medicine Michigan Medicine University Hospitals Ann Arbor Michigan USA

Division of Rheumatology Department of Internal Medicine University of Debrecen Debrecen Hungary

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

Division of Rheumatology Georgetown University Medical Center Washington DC USA

Division of Rheumatology University of Michigan Ann Arbor Michigan USA

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

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

Research and Development Bayer AG 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 The University of Western Ontario London Ontario Canada

StatFinn Oy Espoo Finland

Ann Rheum Dis. 2022 Jul;81(7):e116. doi: 10.1136/annrheumdis-2020-218180. PubMed

Ann Rheum Dis. 2022 Jul;81(7):e117. doi: 10.1136/annrheumdis-2020-218194. PubMed

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