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Safety and efficacy of abatacept in early diffuse cutaneous systemic sclerosis (ASSET): open-label extension of a phase 2, double-blind randomised trial.
Chung, Lorinda; Spino, Cathie; McLain, Richard; Johnson, Sindhu R; Denton, Christopher P; Molitor, Jerry A; Steen, Virginia D; Lafyatis, Robert; Simms, Robert W; Kafaja, Suzanne; Frech, Tracy M; Hsu, Vivien; Domsic, Robyn T; Pope, Janet E; Gordon, Jessica K; Mayes, Maureen D; Sandorfi, Nora; Hant, Faye N; Bernstein, Elana J; Chatterjee, Soumya; Castelino, Flavia V; Ajam, Ali; Allanore, Yannick; Matucci-Cerinic, Marco; Whitfield, Michael L; Distler, Oliver; Singer, Ora; Young, Amber; Nagaraja, Vivek; Fox, David A; Furst, Daniel E; Khanna, Dinesh.
Afiliação
  • Chung L; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Spino C; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • McLain R; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Johnson SR; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Denton CP; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Molitor JA; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Steen VD; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Lafyatis R; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Simms RW; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Kafaja S; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Frech TM; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Hsu V; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Domsic RT; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Pope JE; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Gordon JK; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Mayes MD; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Sandorfi N; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Hant FN; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Bernstein EJ; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Chatterjee S; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Castelino FV; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Ajam A; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Allanore Y; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Matucci-Cerinic M; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Whitfield ML; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Distler O; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Singer O; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Young A; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Nagaraja V; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Fox DA; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Furst DE; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
  • Khanna D; Stanford University School of Medicine, Stanford, CA, USA (Prof L Chung MD); Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA (Prof C Spino ScD, R McLain MS); Division of Rheumatology, Mount Sinai Hospital and University Health Network, Institute of Health Policy, Management a
Lancet Rheumatol ; 2(12): e743-e753, 2020 Dec.
Article em En | MEDLINE | ID: mdl-34966900
ABSTRACT

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 DiffuseCutaneous Systemic Sclerosis), which is a double-blind trial at 22 sites in Canada, the UK, and the USA. Aftercompletion of 12 months of treatment with either abatacept or placebo, patients received a further 6 months ofabatacept (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-labelextension. 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 theabatacept-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.

FUNDING:

Bristol-Myers Squibb and National Institutes of Health.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2020 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2020 Tipo de documento: Article