Lorinda Chung1, Cathie Spino1, Richard McLain1, Sindhu R Johnson1, Christopher P Denton1, Jerry A Molitor1, Virginia D Steen1, Robert Lafyatis1, Robert W Simms1, Suzanne Kafaja1, Tracy M Frech1, Vivien Hsu1, Robyn T Domsic1, Janet E Pope1, Jessica K Gordon1, Maureen D Mayes1, Nora Sandorfi1, Faye N Hant1, Elana J Bernstein1, Soumya Chatterjee1, Flavia V Castelino1, Ali Ajam1, Yannick Allanore1, Marco Matucci-Cerinic1, Michael L Whitfield1, Oliver Distler1, Ora Singer1, Amber Young1, Vivek Nagaraja1, David A Fox1, Daniel E Furst1, Dinesh Khanna1. 1. 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 and Evaluation, University of Toronto, Toronto, ON, Canada (S R Johnson MD); University College London, Division of Medicine, London, UK (Prof C P Denton MD); Rheumatic & Autoimmune Diseases, University of Minnesota, Minneapolis, MN, USA (J A Molitor MD); Rheumatology, Georgetown University Medical Center, Washington, DC, USA (ProfV D Steen MD); Medicine/Division of Rheumatology, Pittsburgh University Medical Center, Pittsburgh, PA, USA (Prof R Lafyatis MD); Rheumatology, Boston University School of Medicine, Boston, MA, USA (Prof R W Simms MD); Rheumatology, Geisel School of Medicine, Dartmouth, Lebanon, NH, USA (Prof R W Simms); Department of Internal Medicine, University of Californiaat Los Angeles, David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA, USA (S Kafaja MD, Prof D E Furst MD); Division of Rheumatology, University of Utah, Salt Lake City, UT, USA (T M Frech MD); Rutgers-Robert Wood Johnson Medical School, Department of Medicine, Rheumatology Division, New Brunswick, NJ, USA (VHsu MD); Medicine-Rheumatology, University of Pittsburgh, Pittsburgh, PA, USA (R T Domsic MD); Department of Medicine, University of Western Ontario, London, ON, Canada (Prof J E Pope MD); Rheumatology, Hospital for Special Surgery, NewYork, NY, USA (J K Gordon MD); McGovern Medical School, University of Texas, Houston, TX, USA (Prof MD Mayes MD); Perelman School of Medicine, University of Pennsylvania, Pittsburgh, PA, USA (N Sandorfi MD); Medicine-Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, USA (F N Hant DO); Rheumatology, Columbia University, New York, NY, USA (E J Bernstein MD); Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH, USA (S Chatterjee MD); Rheumatology, Harvard Medical School, Boston, MA, USA (F V Castelino MD); Division of Rheumatology-Immunology, Ohio State University Wexner Medical Center, Columbus, OH, USA (A Ajam MBBS); Paris Descartes University, Institut National de la Santé et de la Recherche Médicale U1016, Université Sorbonne Paris Cité, and Cochin Hospital, Paris, France (Prof Y Allanore MD); Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology Azienda Ospedaliero Universitaria Careggi, Florence, Italy (Prof M Matucci-Cerinic MD); Geisel School of Medicine at Dartmouth, Hanover, NH, USA (Prof M L Whitfield PhD); Department of Rheumatology, University Hospital, Zurich, Switzerland (Prof O Distler MD); and Division of Rheumatology, Department of Internal Medicine, University of Michigan Scleroderma Program, University of Michigan, Ann Arbor, MI, USA (O Singer MD, A Young MD, V Nagaraja MD, Prof D A Fox MD, Prof D Khanna MD).
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.
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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