Abatacept in Early Diffuse Cutaneous Systemic Sclerosis: Results of a Phase II Investigator-Initiated, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial

Dinesh Khanna, Cathie Spino, Sindhu Johnson, Lorinda Chung, Michael L. Whitfield, Christopher P. Denton, Veronica Berrocal, Jennifer Franks, Bhavan Mehta, Jerry Molitor, Virginia D. Steen, Robert Lafyatis, Robert W. Simms, Anna Gill, Suzanne Kafaja, Tracy M. Frech, Vivien Hsu, Robyn T. Domsic, Janet E. Pope, Jessica K. GordonMaureen D. Mayes, Elena Schiopu, Amber Young, Nora Sandorfi, Jane Park, Faye N. Hant, Elana J. Bernstein, Soumya Chatterjee, Flavia V. Castelino, Ali Ajam, Yue Wang, Tammara Wood, Yannick Allanore, Marco Matucci-Cerinic, Oliver Distler, Ora Singer, Erica Bush, David A. Fox, Daniel E. Furst

Research output: Contribution to journalArticlepeer-review

143 Scopus citations


OBJECTIVE: T cells play a key role in the pathogenesis of early systemic sclerosis. This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc).

METHODS: In this 12-month, randomized, double-blind, placebo-controlled trial, participants were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at 6 months for worsening disease. The coprimary end points were change in the modified Rodnan skin thickness score (MRSS) compared to baseline and safety over 12 months. Differences in longitudinal outcomes were assessed according to treatment using linear mixed models, with outcomes censored after initiation of escape therapy. Skin tissue obtained from participants at baseline was classified into intrinsic gene expression subsets.

RESULTS: Among 88 participants, the adjusted mean change in the MRSS at 12 months was -6.24 units for those receiving abatacept and -4.49 units for those receiving placebo, with an adjusted mean treatment difference of -1.75 units (P = 0.28). Outcomes for 2 secondary measures (Health Assessment Questionnaire disability index and a composite measure) were clinically and statistically significantly better with abatacept. The proportion of subjects in whom escape therapy was needed was higher in the placebo group relative to the abatacept group (36% versus 16%). In the inflammatory and normal-like skin gene expression subsets, decline in the MRSS over 12 months was clinically and significantly greater in the abatacept group versus the placebo group (P < 0.001 and P = 0.03, respectively). In the abatacept group, adverse events occurred in 35 participants versus 40 participants in the placebo group, including 2 deaths and 1 death, respectively.

CONCLUSION: In this phase II trial, abatacept was well-tolerated, but change in the MRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed evidence in support of abatacept. These data should be confirmed in a phase III trial.

Original languageEnglish (US)
Pages (from-to)125-136
Number of pages12
JournalArthritis and Rheumatology
Issue number1
StatePublished - Jan 1 2020

Bibliographical note

Funding Information:
This was an investigator‐initiated trial designed by Dinesh Khanna, MD, MSc, and the Steering Committee. The industry funder, Bristol‐Myers Squibb, had no role in collecting, analyzing, and interpreting the data. Mechanistic studies, including analysis of gene expression in skin biopsies, was funded by the NIH/National Institute of Allergy and Infectious Diseases (NIAID) through the University of Michigan Clinical Autoimmunity Center of Excellence. The data were stored at the University of Michigan. The manuscript was drafted by Drs. Khanna and Spino with input from other coauthors and was reviewed by Bristol‐Myers Squibb and NIH/NIAID before final submission. No medical writer was involved in the creation of the manuscript. Publication of this article was not contingent upon approval by Bristol‐Myers Squibb.

Funding Information:
We wish to thank the participants, study coordinators, statistical analysts (Haoyan Zhong and Richard McLain), and the Data Safety Monitoring Board (Donald Tashkin, MD, Chair, University of California at Los Angeles; Thomas Medsger, Jr., MD, University of Pittsburgh, Pittsburgh, Pennsylvania; and Robert Parker, ScD: Massachusetts General Hospital, Boston).

Publisher Copyright:
© 2019, American College of Rheumatology


  • Abatacept/therapeutic use
  • Adult
  • Double-Blind Method
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Male
  • Middle Aged
  • Patient Reported Outcome Measures
  • Scleroderma, Diffuse/drug therapy
  • Sequence Analysis, RNA
  • Severity of Illness Index
  • Skin/metabolism
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors/therapeutic use
  • Visual Analog Scale
  • Vital Capacity

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Randomized Controlled Trial
  • Multicenter Study
  • Clinical Trial, Phase II
  • Journal Article
  • Research Support, N.I.H., Extramural


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