Subcutaneous abatacept versus intravenous abatacept a phase IIIb noninferiority study in patients with an inadequate response to methotrexate

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 and Rheumatism, 63 10: 2854-2864. doi:10.1002/art.30463

Author 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.
Alten, R.
Title Subcutaneous abatacept versus intravenous abatacept a phase IIIb noninferiority study in patients with an inadequate response to methotrexate
Journal name Arthritis and Rheumatism   Check publisher's open access policy
ISSN 0004-3591
Publication date 2011-10
Sub-type Article (original research)
DOI 10.1002/art.30463
Volume 63
Issue 10
Start page 2854
End page 2864
Total pages 11
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2012
Language eng
Formatted 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.
Keyword Costimulation modulator abatacept
Rheumatoid arthritis
Double blind
Revised criteria
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 67 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 80 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 23 Oct 2011, 00:10:22 EST by System User on behalf of Scholarly Communication and Digitisation Service