Objectives: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors.
Methods: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-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 methotrexate-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 methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (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 methotrexate versus methotrexate alone.
Conclusions: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.
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Funding Editorial assistance was funded by Bristol-Myers Squibb, Princeton, NJ, USA.
Competing interests RW has received consulting fees and speaker’s bureau fees from Bristol-Myers Squibb and Schering-Plough and research support from UCB; ACX was a member of the national board as a consultant for Bristol-Myers Squibb (2003–7) and Abbott (2003–5); JW has received consulting fees from Bristol-Myers Squibb; JG-R is a member of advisory boards for Wyeth, Schering-Plough, Bristol-Myers Squibb and Roche and has received lecture fees from Abbott, Wyeth, Roche, Bristol-Myers Squibb and Schering-Plough; WG is a consultant for Bristol-Myers Squibb, Abbott Immunology, General Electric, Esaote and Schering-Plough, has received honorarium from Bristol-Myers Squibb, Abbott Immunology, General Electric, Schering-Plough and Wyeth and has received research support from Abbott Immunology and Wyeth; BH is a consultant and has received a grant/research support for Abbott Canada, Amgen Canada, Bristol-Myers Squibb Canada, Roche and Schering-Plough; WS is a speaker and principal investigator for Amgen, Wyeth, Abbott, Bristol-Myers Squibb, Centocor, Genentech and Biogen Idec; HG is a consultant for CCBR-SYNARC, Bristol-Myers Squibb, Wyeth, Roche, Servier, GlaxoSmithKline, Merck, Biogen Idec and Genentech and has stocks in CCBR-SYNARC; CP is an employee and has stocks in Synarc Inc; J-CB is an employee of BMS and owns stock options; AC and RH are employees of Bristol-Myers Squibb; JB is a consultant for Centocor and Riley, is on the advisory board for Abbott and Amgen, has received research support for Amgen, Biogen Idec and Bristol-Myers Squibb and has received honorarium for Abbott, Amgen, Centocor and Novartis. MR, SN, PD and SHP have nothing to disclose.
Ethics approval The protocol and patients’ informed consent received institutional review board/independent ethics committee approval, and the study was conducted in accordance with the Declaration of Helsinki and was consistent with International Conference on Harmonisation good clinical practice.
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