Rheumatoid Arthritis

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Subcutaneous abatacept versus intravenous abatacept: A phase IIIb noninferiority study in patients with an inadequate response to methotrexate†‡

  1. M. C. Genovese1,§,*,
  2. A. Covarrubias2,
  3. G. Leon3,
  4. E. Mysler4,§,
  5. M. Keiserman5,§,
  6. R. Valente6,§,
  7. P. Nash7,§,
  8. J. A. Simon-Campos8,
  9. W. Porawska9,
  10. J. Box10,§,
  11. C. Legerton III11,§,
  12. E. Nasonov12,
  13. P. Durez13,¶,
  14. R. Aranda14,‖,
  15. R. Pappu14,‖,
  16. I. Delaet14,
  17. J. Teng14,‖,
  18. R. Alten15,††

Article first published online: 27 SEP 2011

DOI: 10.1002/art.30463

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 63, Issue 10, pages 2854–2864, October 2011

Additional Information

How to Cite

Genovese, M. C., Covarrubias, A., Leon, G., Mysler, E., Keiserman, M., Valente, R., Nash, P., Simon-Campos, J. A., Porawska, W., Box, J., Legerton, C., Nasonov, E., Durez, P., Aranda, R., Pappu, R., Delaet, I., Teng, J. and Alten, R. (2011), Subcutaneous abatacept versus intravenous abatacept: A phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis & Rheumatism, 63: 2854–2864. doi: 10.1002/art.30463

Author Information

  1. 1

    Stanford University, Palo Alto, California

  2. 2

    Centro Medico De Las Americas, Merida, Mexico

  3. 3

    Instituto De Ginecologia Y Reproduccion, Lima, Peru

  4. 4

    Organización Médica de Investigación, Buenos Aires, Argentina

  5. 5

    Pontificial Catholic University School of Medicine, Porto Alegre, Brazil

  6. 6

    Physician Research Collaboration, Lincoln, Nebraska

  7. 7

    University of Queensland, Brisbane, Queensland, Australia

  8. 8

    Centro De Especialidades Médicas/HRAEPY, Merida, Mexico

  9. 9

    Poznanski Osrodek Medyczny Novamed, Poznań, Poland

  10. 10

    Box Arthritis and Rheumatology of the Carolinas, Charlotte, North Carolina

  11. 11

    Low Country Rheumatology, Charleston, South Carolina

  12. 12

    Institute of Rheumatology, Moscow, Russia

  13. 13

    Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium

  14. 14

    Bristol-Myers Squibb, Princeton, New Jersey

  15. 15

    Schlosspark-Klinik, Teaching Hospital of the Charité University Medicine Berlin, Berlin, Germany

  1. §

    Drs. Genovese, Mysler, Keiserman, Valente, Nash, Box, and Legerton have received honoraria from Bristol-Myers Squibb (less than $10,000).

  2. Dr. Durez has received honoraria from Bristol-Myers Squibb, Pfizer, Abbott, UCB, and MSD (less than $10,000 each).

  3. ‖

    Drs. Aranda, Pappu, and Teng own stock or stock options in Bristol-Myers Squibb.

  4. ††

    Dr. Alten has received honoraria from Abbott, Bristol-Myers Squibb, Horizon Pharma, Merck, Nitec Pharma, Novartis, and Roche (less than $10,000 each).

*Stanford University, Division of Immunology and Rheumatology, 1000 Welch Road, Suite 203, Palo Alto, CA 94304

  1. †

    ClinicalTrials.gov identifier: NCT00559585.

  2. ‡

    Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms

  3. §

    Drs. Genovese, Mysler, Keiserman, Valente, Nash, Box, and Legerton have received honoraria from Bristol-Myers Squibb (less than $10,000).

  4. Dr. Durez has received honoraria from Bristol-Myers Squibb, Pfizer, Abbott, UCB, and MSD (less than $10,000 each).

  5. ‖

    Drs. Aranda, Pappu, and Teng own stock or stock options in Bristol-Myers Squibb.

  6. ††

    Dr. Alten has received honoraria from Abbott, Bristol-Myers Squibb, Horizon Pharma, Merck, Nitec Pharma, Novartis, and Roche (less than $10,000 each).

Publication History

  1. Issue published online: 27 SEP 2011
  2. Article first published online: 27 SEP 2011
  3. Accepted manuscript online: 25 MAY 2011 11:01AM EST
  4. Manuscript Accepted: 17 MAY 2011
  5. Manuscript Received: 6 JAN 2011

Funded by

  • Bristol-Myers Squibb

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Abstract

Objective

To compare the efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept.

Methods

In this phase IIIb double-blind, double-dummy, 6-month study, patients with rheumatoid arthritis (RA) and inadequate responses to methotrexate were randomized to receive 125 mg SC abatacept on days 1 and 8 and weekly thereafter (plus an IV loading dose [∼10 mg/kg] on day 1) or IV abatacept (∼10 mg/kg) on days 1, 15, and 29 and every 4 weeks thereafter. The primary end point for determining the noninferiority of SC abatacept to IV abatacept was the proportion of patients in each group meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at month 6. Other efficacy end points, immunogenicity, and safety were also assessed.

Results

Of 1,457 patients, 693 of 736 (94.2%) treated with SC abatacept and 676 of 721 (93.8%) treated with IV abatacept completed 6 months. At month 6, 76.0% (95% confidence interval 72.9, 79.2) of SC abatacept–treated patients versus 75.8% (95% confidence interval 72.6, 79.0) of IV abatacept–treated patients achieved an ACR20 response (estimated difference between groups 0.3% [95% confidence interval –4.2, 4.8]), confirming noninferiority of SC abatacept to IV abatacept. Onset and magnitude of ACR responses and disease activity and physical function improvements were comparable between the SC and IV abatacept–treated groups. The proportions of adverse events (AEs) and serious AEs over 6 months were 67.0% and 4.2%, respectively, in the SC abatacept–treated group and 65.2% and 4.9%, respectively, in the IV abatacept–treated group, with comparable frequencies of serious infections, malignancies, and autoimmune events between groups. SC injection site reactions (mostly mild) occurred in 19 SC abatacept (IV placebo)–treated patients (2.6%) and 18 IV abatacept (SC placebo)–treated patients (2.5%). Abatacept-induced antibodies occurred in 1.1% of SC abatacept–treated patients and 2.3% of IV abatacept–treated patients.

Conclusion

SC abatacept provides efficacy and safety comparable with that of IV abatacept, with low immunogenicity and high retention rates, consistent with the established IV abatacept profile. Rates of injection site reactions were low. SC abatacept will provide additional treatment options, such as an alternative route of administration, for patients with RA.

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