Objectives: To assess the efficacy and safety of abatacept in methotrexate (MTX)-naïve patients with early rheumatoid arthritis (RA) and poor prognostic factors.
Methods: In this double-blind, Phase IIIb study, patients with RA ≤2 years were randomized 1:1 to receive abatacept (~10 mg/kg) plus MTX, or placebo plus MTX. Patients were MTX-naïve and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) 2 or both, and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving Disease Activity Score (DAS) 28-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score [TS]) at Year 1. Safety was monitored throughout.
Results: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5 and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At Year 1, a significantly greater proportion of abatacept plus MTX-treated patients achieved remission (41.4 vs 23.3%; p<0.001), and there was significantly less radiographic progression (mean change in TS; 0.63 vs 1.06; p=0.040), versus MTX alone. Over 1 year, the frequency of adverse events (AEs; 84.8 vs 83.4%), serious AEs (7.8 vs 7.9%), serious infections (2.0 vs 2.0%), autoimmune disorders (2.3 vs 2.0%) and malignancies (0.4 vs 0%) was comparable for abatacept plus MTX versus MTX alone.
Conclusions: In a MTX-naïve population with early RA and poor prognostic factors, the combination of abatacept and MTX provided significantly better clinical and radiographic efficacy compared with MTX alone, and had a comparable, favorable safety profile.