Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
A Large, Phase IIIb Non-Inferiority Trial of Subcutaneous (SC) Abatacept Compared with Intravenous (IV) Abatacept, in Patients with Rheumatoid Arthritis (RA).
Genovese13, Mark C., Covarrubias3, Jose Arturo, Leon5, Gustavo, Mysler8, Eduardo F., Keiserman10, Mauro W., Valente9, Robert M., Nash15, Peter
Bristol-Myers Squibb Co, Princeton, NJ
Pontificial Catholic University, School of Medicine, Porto Alegre, Brazil
Poznanski Osrodek Medyczny Novamed, Ponzan, Poland
Schlosspark-Klinik, Charité, University Medicine Berlin, Department of Internal Medicine II Rheumatology, Berlin, Germany
Stanford University, Palo Alto, Sunnyvale, CA
The Arthritis Clinic & Carolina Bone & Joint, Charlotte, NC
University of Queensland, Brisbane, Australia
Centro de Especialidades Médicas, Merida, Mexico
Centro Medico de Las Americas, Merida, Yucatan, Mexico
Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
De Ginecologia Y Reproduccion, Lima, Peru
Department of Medicine, Medical University of South Carolina, Charleston, SC
Institute of Rheumatology, Moscow, Russia
Organización Médica de Investigación, Buenos Aires, Argentina
Physician Research Collaboration, Lincoln, Lincoln, NE
The efficacy and safety of IV abatacept has been well established in patients with RA;1,2 an SC abatacept formulation will provide additional treatment options. Here we compare the efficacy and safety of SC and IV abatacept.
This was a Phase IIIb, double-blind, double dummy study of patients with active RA (>=10 swollen and >=12 tender joints, CRP >=0.8 mg/dL) and inadequate response to MTX. Patients were randomized to weekly SC abatacept (125 mg) injections with added IV loading (~10 mg/kg) on Day 1, or IV abatacept (~10 mg/kg) on Days 1, 15, 29 and every 4 weeks thereafter, plus MTX (<=15 mg/week), for 6 months. The primary objective was to determine non-inferiority of SC to IV abatacept, by difference in ACR 20 response at Month 6. Secondary endpoints included ACR 50 and 70 responses, physical function (HAQ-DI response; improvement from baseline of >=0.3) and immunogenicity (ELISA). Efficacy was assessed for both per protocol (PP) and intent to treat (ITT) populations. Patients who received >=1 dose of abatacept were monitored for safety.
Of 1457 randomized and treated patients, 693/736 (94.2%) SC and 676/721 (93.8%) IV patients remained on treatment at Month 6; 78 patients deviated protocol. Mean baseline characteristics were similar between groups (PP population): RA duration was 7.7 years; tender and swollen joint counts were 29.6 and 20.0; HAQ-DI was 1.7. At Month 6, 76.1% (95% CI: 73.0, 79.3) of SC vs 75.7% (72.5, 78.9) of IV patients achieved ACR 20, with an estimated difference (95% CI) of 0.3 (4.2, 4.8) confirming non-inferiority of SC abatacept to IV abatacept. ACR responses over time were comparable (Figure). At Month 6, similar proportions of SC and IV patients achieved HAQ-DI response; 69.8 (66.4, 73.2) and 65.0% (61.4, 68.6), respectively. Results were consistent for PP and ITT populations. Frequencies of AEs and serious AEs over 6 months were comparable for SC versus IV (67.0 vs 65.2% and 4.2 vs 4.9%, respectively). Events of interest were comparable in the SC versus IV groups, respectively (serious infections in 5 [0.7%] vs 10 [1.4%], most common being pneumonia [1 vs 3]; malignancies in 3 [0.4%] vs 5 [0.7%], most common being basal cell carcinoma [2 vs 1]; pre-specified autoimmune events in 7 [1.0%] vs 6 [0.8%], most common being psoriasis [2 vs 4]). Local injection site reactions occurred in 19 (2.6%) SC and 18 (2.5%) IV patients; most were mild. Abatacept-induced antibodies were observed in 1.1 and 2.3% of SC and IV patients, respectively, and did not affect safety, efficacy or pharmacokinetics.
Consistent with the established IV abatacept profile, SC abatacept provides comparable efficacy and safety, with low immunogenicity and high retention rates; injection site reactions were few and mild. SC abatacept will provide additional treatment options for RA patients.
To cite this abstract, please use the following information:
Genovese, Mark C., Covarrubias, Jose Arturo, Leon, Gustavo, Mysler, Eduardo F., Keiserman, Mauro W., Valente, Robert M., et al; A Large, Phase IIIb Non-Inferiority Trial of Subcutaneous (SC) Abatacept Compared with Intravenous (IV) Abatacept, in Patients with Rheumatoid Arthritis (RA). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2173