Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc): randomised, double-blind, placebo-controlled multicentre trial

Khanna, Dinesh; Allanore, Yannick; Denton, Christopher P; Kuwana, Masataka; Matucci-Cerinic, Marco; Pope, Janet E; Atsumi, Tatsuya; Becvar, Radim; Czirjak, Laszlo; Hachulla, Eric; Ishii, Tomonori; Ishikawa, Osamu; Johnson, Sindhu R; De Langhe, Ellen; Stagnaro, Chiara; Riccieri, Valeria; Schiopu, Elena; Silver, Richard M; Smith, Vanessa; Steen, Virginia; Stevens, Wendy; Szucs, Gabriella; Truchetet, Marie-Elise; Wosnitza, Melanie; Laapas, Kaisa; Pena, Janethe de Oliveira; Yao, Zhen; Kramer, Frank; Distler, Oliver

doi:10.1136/annrheumdis-2019-216823

Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc): randomised, double-blind, placebo-controlled multicentre trial

Author:

Khanna, Dinesh

Allanore, Yannick ; Denton, Christopher P ; Kuwana, Masataka ; Matucci-Cerinic, Marco ; Pope, Janet E ; Atsumi, Tatsuya ; Becvar, Radim ; Czirjak, Laszlo ; Hachulla, Eric ; Ishii, Tomonori ; Ishikawa, Osamu ; Johnson, Sindhu R ; De Langhe, Ellen ; Stagnaro, Chiara ; Riccieri, Valeria ; Schiopu, Elena ; Silver, Richard M ; Smith, Vanessa ; Steen, Virginia ; Stevens, Wendy ; Szucs, Gabriella ; Truchetet, Marie-Elise ; Wosnitza, Melanie ; Laapas, Kaisa ; Pena, Janethe de Oliveira ; Yao, Zhen ; Kramer, Frank ; Distler, Oliver

Keywords:

Science & Technology, Life Sciences & Biomedicine, Rheumatology, SOLUBLE GUANYLATE-CYCLASE, CLINICAL-TRIALS, SKIN FIBROSIS, AMERICAN-COLLEGE, SCORE, CLASSIFICATION, STIMULATION, PREDICTION, CRITERIA, disease activity, systemic sclerosis, treatment, Adult, Biopsy, Needle, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Enzyme Activators, Female, Follow-Up Studies, Humans, Immunohistochemistry, Internationality, Male, Middle Aged, Pyrazoles, Pyrimidines, Respiratory Function Tests, Risk Assessment, Scleroderma, Diffuse, Severity of Illness Index, Treatment Failure, 1103 Clinical Sciences, 1107 Immunology, 1117 Public Health and Health Services, Arthritis & Rheumatology, 3202 Clinical sciences, 3204 Immunology

Abstract:

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.