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Efficacy and safety of abatacept in active primary Sjögren’s syndrome: results of a phase III, randomised, placebo-controlled trial
  1. Alan N Baer1,
  2. Jacques-Eric Gottenberg2,
  3. E William St Clair3,
  4. Takayuki Sumida4,
  5. Tsutomu Takeuchi5,
  6. Raphaèle Seror6,
  7. Gary Foulks7,
  8. Marleen Nys8,
  9. Sumanta Mukherjee9,
  10. Robert Wong10,
  11. Neelanjana Ray11,
  12. Hendrika Bootsma12
  1. 1 Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  2. 2 Department of Rheumatology, Strasbourg University Hospitals, National Reference Center for Rare Systemic Autoimmune Diseases, IBMC, CNRS, UPR3572, Strasbourg, France
  3. 3 Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
  4. 4 Department of Internal Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
  5. 5 Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
  6. 6 Department of Rheumatology and National Reference Center for Sjögren Syndrome and Rare Autoimmune Diseases, AP-HP Université Paris-Saclay, INSERM UMR1184, Le Kremlin Bicêtre, Paris, France
  7. 7 Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, Kentucky, USA
  8. 8 Global Biometric Sciences, Bristol Myers Squibb, Braine L’Alleud, Belgium
  9. 9 Innovative Medicines and Development – Clinical Biomarkers, Bristol Myers Squibb Company, Princeton, New Jersey, USA
  10. 10 Immunology and Fibrosis, Bristol Myers Squibb Company, Princeton, New Jersey, USA
  11. 11 Global Drug Development – Immunology, Bristol Myers Squibb Company, Princeton, New Jersey, USA
  12. 12 Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  1. Correspondence to Dr Alan N Baer, 5200 Eastern Avenue, Mason Lord Center Tower, Suite 4000, Baltimore, MD 21224, USA; alanbaer{at}


Objectives To evaluate efficacy and safety of abatacept in adults with active primary Sjögren’s syndrome (pSS) in a phase III, randomised, double-blind, placebo-controlled trial.

Methods Eligible patients (moderate-to-severe pSS [2016 ACR/European League Against Rheumatism (EULAR) criteria], EULAR Sjögren’s Syndrome Disease Activity Index [ESSDAI] ≥5, anti-SS-related antigen A/anti-Ro antibody positive) received weekly subcutaneous abatacept 125 mg or placebo for 169 days followed by an open-label extension to day 365. Primary endpoint was mean change from baseline in ESSDAI at day 169. Key secondary endpoints were mean change from baseline in EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and stimulated whole salivary flow (SWSF) at day 169. Other secondary clinical endpoints included glandular functions and patient-reported outcomes. Selected biomarkers and immune cell phenotypes were examined. Safety was monitored.

Results Of 187 patients randomised, 168 completed double-blind period and 165 continued into open-label period. Mean (SD) baseline ESSDAI and ESSPRI total scores were 9.4 (4.3) and 6.5 (2.0), respectively. Statistical significance was not reached for primary (ESSDAI −3.2 abatacept vs −3.7 placebo, p=0.442) or key secondary endpoints (ESSPRI, p=0.337; SWSF, p=0.584). No clinical benefit of abatacept over placebo at day 169 was seen with other clinical and PRO endpoints. Relative to baseline, abatacept was associated with significant differences vs placebo in some disease-relevant biomarkers (including IgG, IgA, IgM-rheumatoid factor) and pathogenic cell subpopulations (post hoc analyses). No new safety signals were identified.

Conclusions Abatacept treatment did not result in significant clinical efficacy compared with placebo in patients with moderate-to-severe pSS, despite evidence of biological activity.

  • autoimmune diseases
  • Sjogren's syndrome
  • therapeutics

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  • Handling editor Josef S Smolen

  • Contributors All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. All authors are accountable for all aspects of the work and will ensure questions related to the accuracy or integrity of any part of the work will be appropriately investigated and resolved. Study conception and design: ANB, J-EG, EWSC, TT, GF, MN, RW and NR. Acquisition of data: EWSC, TS, RS, GF, SM, RW and NR. Analysis and interpretation: ANB, J-EG, EWSC, TT, RS, GF, MN, SM, RW, NR and HB.

  • Funding This study was sponsored by Bristol Myers Squibb Company.

  • Competing interests ANB: Consultant: Bristol Myers Squibb Company, Sanofi, VielaBio; Fees: UpToDate; Clinical trials: VielaBio, Novartis. J-EG: Grant/research support: Bristol Myers Squibb Company; Consultant: Bristol Myers Squibb Company, Lilly, UCB, Sanofi-Genzyme, Pfizer. EWSC: Consulting fees and grant/research support: Bristol Myers Squibb Company; Consulting fees: AbbVie, VielaBio. TS: Grant/research support and Speakers’ bureau: Bristol Myers Squibb Company. TT: Grant/Research: AbbVie, Asahi Kasei, Astellas, AYUMI, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Nipponkayaku, Novartis, Pfizer Japan, Takeda; Consultant: AbbVie, Astellas, Astra Zeneca, Chugai, Eli Lilly Japan, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Nipponkayaku, Novartis, Taiho, Taisho Toyama, UCB Japan; Speakers’ bureau: AbbVie, Astellas, Bristol Myers Squibb Company, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Novartis, Pfizer Japan, Sanofi, Takeda, Teijin. RS: Grant/research support: Pfizer; Consultant: Amgen, Bristol Myers Squibb Company, Celgene, GlaxoSmithKline, Lilly, Pfizer, Roche. GF: Consultant: Aldeyra, Allysta, Aurinia, Bristol Myers Squibb Company, Clemencia, Hovione, Kala, Lexitas PharmaServices, Nicox, Noveome, Sight Sciences, Tarsus, Tear Solutions; Stock: TearLab. MN: Employee: Bristol Myers Squibb Company; Shareholder: Bristol Myers Squibb Company. SM: Employee: Bristol Myers Squibb Company; Shareholder: Bristol Myers Squibb Company. RW: Employee: Bristol Myers Squibb Company; Shareholder: Bristol Myers Squibb Company. NR: Employee: Bristol Myers Squibb Company; Shareholder: Bristol Myers Squibb Company. HB: Unrestricted grant: Bristol Myers Squibb Company, Roche; Consultant: Speakers bureau: Bristol Myers Squibb Company, Novartis.

  • Patient consent for publication Not required.

  • Ethics approval This study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice guidelines. The study protocol and patient enrolment materials were approved by local ethics committees and institutional review boards prior to study initiation.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplemental information. Bristol Myers Squibb policy on data sharing may be found at

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.