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

被引：81

作者：

Khanna, Dinesh ^{[1
]}

Allanore, Yannick ^{[2
]}

Denton, Christopher P. ^{[3
]}

Kuwana, Masataka ^{[4
]}

Matucci-Cerinic, Marco ^{[5
]}

Pope, Janet E. ^{[6
]}

Atsumi, Tatsuya ^{[7
,8
]}

Becvar, Radim ^{[9
]}

Czirjak, Laszlo ^{[10
]}

Hachulla, Eric ^{[11
]}

Ishii, Tomonori ^{[12
]}

Ishikawa, Osamu ^{[13
]}

Johnson, Sindhu R. ^{[14
]}

De Langhe, Ellen ^{[15
]}

Stagnaro, Chiara ^{[16
]}

Riccieri, Valeria ^{[17
]}

Schiopu, Elena ^{[18
]}

Silver, Richard M. ^{[19
]}

Smith, Vanessa ^{[20
]}

Steen, Virginia ^{[21
]}

Stevens, Wendy ^{[22
]}

Szucs, Gabriella ^{[23
]}

Truchetet, Marie-Elise ^{[24
]}

Wosnitza, Melanie ^{[25
]}

Laapas, Kaisa ^{[26
]}

Pena, Janethe de Oliveira ^{[27
]}

Yao, Zhen ^{[28
]}

Kramer, Frank ^{[25
]}

Distler, Oliver ^{[29
]}

机构：

[1] Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA

[2] Paris Descartes Univ, Cochin Hosp, APHP, Rheumatol Dept A, Paris, France

[3] UCL, Div Med, Ctr Rheumatol, London, England

[4] Nippon Med Sch, Grad Sch Med, Dept Allergy & Rheumatol, Tokyo, Japan

[5] Univ Florence, Dept Expt & Clin Med, Florence, Italy

[6] Univ Western Ontario, Schulich Sch Med, Div Rheumatol, London, ON, Canada

[7] Hokkaido Univ, Fac Med, Dept Rheumatol Endocrinol & Nephrol, Sapporo, Hokkaido, Japan

[8] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan

[9] Charles Univ Prague, Inst Rheumatol, Dept Rheumatol, Fac Med 1, Prague, Czech Republic

[10] Univ Pecs, Dept Rheumatol & Immunol, Pecs, Hungary

[11] Lille Univ, Dept Internal Med & Clin Immunol, Claude Huriez Hosp, Sch Med, Lille, France

[12] Tohoku Univ Hosp, Clin Res Innovat & Educ Ctr, Sendai, Miyagi, Japan

[13] Gunma Univ, Postgrad Sch Med, Dept Dermatol, Maebashi, Gunma, Japan

[14] Univ Toronto, Toronto Scleroderma Res Program, Toronto Western Hosp, Div Rheumatol,Dept Med,Univ Hlth Network,Mt Sinai, Toronto, ON, Canada

[15] Katholieke Univ Leuven, Lab Tissue Homeostasis & Dis, Skeletal Biol & Engn Res Ctr, Dept Dev & Regenerat, Leuven, Belgium

[16] Univ Pisa, Dept Clin & Expt Med, Rheumatol Unit, Pisa, Italy

[17] Univ Roma La Sapienza, Dept Clin Med & Therapy, Rome, Italy

[18] Michigan Med Univ Hosp, Dept Internal Med, Div Rheumatol, Ann Arbor, MI USA

[19] Med Univ South Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA

[20] Ghent Univ Hosp, Dept Rheumatol & Internal Med, Ghent, Belgium

[21] Georgetown Univ, Med Ctr, Div Rheumatol, Washington, DC 20007 USA

[22] St Vincents Hosp Melbourne, Dept Rheumatol, Melbourne, Vic, Australia

[23] Univ Debrecen, Dept Internal Med, Div Rheumatol, Debrecen, Hungary

[24] CHU Bordeaux, Dept Rheumatol, Bordeaux, France

[25] Bayer AG, Res & Dev, Wuppertal, Germany

[26] StatFinn Oy, Espoo, Finland

[27] Bayer HealthCare Pharmaceut Inc, Whippany, NJ USA

[28] Bayer Healthcare, Beijing, Peoples R China

[29] Univ Hosp, Dept Rheumatol, Zurich, Switzerland

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2020年 / 79卷 / 05期

关键词：

SOLUBLE GUANYLATE-CYCLASE; CLINICAL-TRIALS; SKIN FIBROSIS; AMERICAN-COLLEGE; SCORE; CLASSIFICATION; STIMULATION; PREDICTION; CRITERIA;

D O I：

10.1136/annrheumdis-2019-216823

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：618 / 625

页数：8

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