A phase IIIb double-blind, double-dummy, 6-month study, patients with rheumatoid arthritis (RA) and inadequate responses to methotrexate to compare the efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept «Genovese MC, Covarrubias A, Leon G ym. Subcutaneou...»1. The rheumatoid arthritis patients (ACR 1987 revised criteria for RA) 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.
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). 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.
Bristol-Myers Squibb employees (as authors) were involved in the study design, data collection, analysis, review, and approval of the manuscript, and Bristol-Myers Squibb funded the editorial support.