TY - JOUR
T1 - Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc)
T2 - Randomised, double-blind, placebo-controlled multicentre trial
AU - Khanna, Dinesh
AU - Allanore, Yannick
AU - Denton, Christopher P.
AU - Kuwana, Masataka
AU - Matucci-Cerinic, Marco
AU - Pope, Janet E.
AU - Atsumi, Tatsuya
AU - Bečvár, Radim
AU - Czirják, László
AU - Hachulla, Eric
AU - Ishii, Tomonori
AU - Ishikawa, Osamu
AU - Johnson, Sindhu R.
AU - De Langhe, Ellen
AU - Stagnaro, Chiara
AU - Riccieri, Valeria
AU - Schiopu, Elena
AU - Silver, Richard M.
AU - Smith, Vanessa
AU - Steen, Virginia
AU - Stevens, Wendy
AU - Szücs, Gabriella
AU - Truchetet, Marie Elise
AU - Wosnitza, Melanie
AU - Laapas, Kaisa
AU - De Oliveira Pena, Janethe
AU - Yao, Zhen
AU - Kramer, Frank
AU - Distler, Oliver
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2020.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
KW - disease activity
KW - systemic sclerosis
KW - treatment
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UR - http://www.scopus.com/inward/citedby.url?scp=85083523148&partnerID=8YFLogxK
U2 - 10.1136/annrheumdis-2019-216823
DO - 10.1136/annrheumdis-2019-216823
M3 - Article
C2 - 32299845
AN - SCOPUS:85083523148
SN - 0003-4967
VL - 79
SP - 618
EP - 625
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 5
ER -