Safety and efficacy of abatacept in early diffuse cutaneous systemic sclerosis (ASSET): open-label extension of a phase 2, double-blind randomised trial

被引：31

作者：

Chung, Lorinda ^{[1
]}

Spino, Cathie ^{[2
]}

McLain, Richard ^{[2
]}

Johnson, Sindhu R. ^{[3
,4
]}

Denton, Christopher P. ^{[5
]}

Molitor, Jerry A. ^{[6
]}

Steen, Virginia D. ^{[7
]}

Lafyatis, Robert ^{[8
]}

Simms, Robert W. ^{[9
,10
]}

Kafaja, Suzanne ^{[11
]}

Frech, Tracy M. ^{[11
,12
]}

Hsu, Vivien ^{[13
]}

Domsic, Robyn T. ^{[14
]}

Pope, Janet E. ^{[15
]}

Gordon, Jessica K. ^{[16
]}

Mayes, Maureen D. ^{[17
]}

Sandorfi, Nora ^{[18
]}

Hant, Faye N. ^{[19
]}

Bernstein, Elana J. ^{[20
]}

Chatterjee, Soumya ^{[21
]}

Castelino, Flavia V. ^{[22
]}

Ajam, Ali ^{[23
]}

Allanore, Yannick ^{[24
,25
]}

Matucci-Cerinic, Marco ^{[26
,27
]}

Whitfield, Michael L. ^{[28
]}

Distler, Oliver ^{[29
]}

Singer, Ora ^{[30
]}

Young, Amber ^{[30
]}

Nagaraja, Vivek ^{[30
]}

Fox, David A. ^{[30
]}

Furst, Daniel E. ^{[11
]}

Khanna, Dinesh ^{[30
]}

机构：

[1] Stanford Univ, Sch Med, Stanford, CA 94305 USA

[2] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA

[3] Univ Toronto, Mt Sinai Hosp, Div Rheumatol, Toronto, ON, Canada

[4] Univ Toronto, Univ Hlth Network, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada

[5] UCL, Div Med, London, England

[6] Univ Minnesota, Rheumat & Autoimmune Dis, Minneapolis, MN USA

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

[8] Pittsburgh Univ, Med Ctr, Med Div Rheumatol, Pittsburgh, PA USA

[9] Boston Univ, Sch Med, Rheumatol, Boston, MA 02118 USA

[10] Geisel Sch Med, Rheumatol, Lebanon, NH USA

[11] Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Div Rheumatol, Los Angeles, CA 90095 USA

[12] Univ Utah, Div Rheumatol, Salt Lake City, UT USA

[13] Rutgers Robert Wood Johnson Med Sch, Dept Med, Rheumatol Div, New Brunswick, NJ USA

[14] Univ Pittsburgh, Med Rheumatol, Pittsburgh, PA USA

[15] Univ Western Ontario, Dept Med, London, ON, Canada

[16] Hosp Special Surg, Rheumatol, 535 E 70th St, New York, NY 10021 USA

[17] Univ Texas Houston, McGovern Med Sch, Houston, TX USA

[18] Univ Penn, Perelman Sch Med, Pittsburgh, PA USA

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

[20] Columbia Univ, Rheumatol, New York, NY USA

[21] Cleveland Clin, Rheumat & Immunol Dis, Cleveland, OH 44106 USA

[22] Harvard Med Sch, Rheumatol, Boston, MA 02115 USA

[23] Ohio State Univ, Wexner Med Ctr, Div Rheumatol Immunol, Columbus, OH 43210 USA

[24] Univ Sorbonne Paris Cite, Paris Descartes Univ, INSERM, U1016, Paris, France

[25] Cochin Hosp, Paris, France

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

[27] Azienda Osped Univ Careggi, Div Rheumatol, Florence, Italy

[28] Geisel Sch Med Dartmouth, Hanover, NH USA

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

[30] Univ Michigan, Dept Internal Med, Scleroderma Program, Div Rheumatol, Ann Arbor, MI 48109 USA

来源：

LANCET RHEUMATOLOGY | 2020年 / 2卷 / 12期

基金：

美国国家卫生研究院;

关键词：

STEM-CELL TRANSPLANTATION; AMERICAN-COLLEGE; CLINICAL-TRIALS; RISE-SSC; PLACEBO; TOCILIZUMAB; CLASSIFICATION; RIOCIGUAT; CRITERIA; SKIN;

D O I：

10.1016/S2665-9913(20)30237-X

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Abatacept was well tolerated by patients with early diffuse cutaneous systemic sclerosis in a phase 2, double-blind randomised trial, with potential efficacy at 12 months. We report here the results of an open-label extension for 6 months. Methods Patients (aged >= 18 years) with diffuse cutaneous systemic sclerosis of less than 3 years' duration from their first non-Raynaud's symptom were enrolled into the ASSET trial (A Study of Subcutaneous Abatacept to Treat Diffuse Cutaneous Systemic Sclerosis), which is a double-blind trial at 22 sites in Canada, the UK, and the USA. After completion of 12 months of treatment with either abatacept or placebo, patients received a further 6 months of abatacept (125 mg subcutaneous every week) in an open-label extension. The primary endpoint of the double-blind trial was modified Rodnan Skin Score (mRSS) at 12 months, which was reassessed at 18 months in the open-label extension. The primary analysis included all participants who completed the double-blind trial and received at least one dose of open-label treatment (modified intention to treat). This trial is registered with ClinicalTrials.gov, NCT02161406. Findings Between Sept 22, 2014, and March 15, 2017, 88 participants were randomly allocated in the double-blind trial either abatacept (n=44) or placebo (44); 32 patients from each treatment group completed the 6-month open-label extension. Among patients assigned abatacept, a mean improvement from baseline in mRSS was noted at 12 months (-6.6 [SD 6.4]), with further improvement seen during the open-label extension period (-9.8 [8.1] at month 18). Participants assigned placebo had a mean improvement from baseline in mRSS at 12 months (-3.7 [SD 7.6]), with a further improvement at month 18 (-6.3 [9.3]). Infections during the open-label extension phase occurred in nine patients in the placebo-abatacept group (12 adverse events, one serious adverse event) and in 11 patients in the abatacept-abatacept group (14 adverse events, one serious adverse event). Two deaths occurred during the 12-month double-blind period in the abatacept group, which were related to scleroderma renal crisis; no deaths were recorded during the open-label extension. Interpretation During the 6-month open-label extension, no new safety signals for abatacept were identified in the treatment of diffuse cutaneous systemic sclerosis. Clinically meaningful improvements in mRSS and other outcome measures were observed in both the abatacept and placebo groups when patients transitioned to open-label treatment. These data support further studies of abatacept in diffuse cutaneous systemic sclerosis. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

引用

页码：E743 / E753

页数：11

共 39 条

[1] Systemic sclerosis phase III clinical trials: Hope on the horizon? [J].