Objective To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA).
Methods The AGREE was a 2-year phase IIIb multinational study in early (≤2 years) RA. During the double-blind period (year 1), patients were randomly assigned 1:1 to receive abatacept+methotrexate or methotrexate alone; all patients received open-label abatacept+methotrexate during year 2. Clinical outcomes assessed included 28-joint disease activity score (DAS28) defined remission, low disease activity score (LDAS), American College of Rheumatology (ACR) responses and physical function. Radiographic outcomes were assessed using the Genant-modified Sharp total score (TS). Safety was monitored throughout.
Results Of the 459 patients completing year 1, 433 patients (94.3%) completed year 2. DAS28-defined remission, LDAS, ACR and physical function were sustained through year 2 in the original abatacept+methotrexate group, with 55.2% in remission at 2 years. Upon introduction of abatacept in the methotrexate-alone group, additional patients achieved DAS28-defined remission (44.5% vs 26.9%), LDAS (60.4% vs 43.2%) and improved ACR 70 (49.8% vs 31.7%) for year 2 versus year 1. Less radiographic progression was observed at 2 years in the original abatacept+methotrexate group than the methotrexate-alone group (change in TS 0.84 vs 1.75, p<0.001). No new safety issues were seen. Similar rates of serious adverse events, serious infections and autoimmune events were observed in years 1 and 2.
Conclusions The AGREE trial was the first to examine the impact of T-cell co-stimulation modulation with abatacept in patients with early erosive RA. Early treatment with abatacept+methotrexate resulted in greater sustainable clinical, functional and radiographic benefits than methotrexate alone, with acceptable safety and tolerability.
Trial Registration: NCT00122382
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Funding Bristol-Myers Squibb funded the AGREE trial. Editorial assistance was funded by Bristol-Myers Squibb, Princeton, New Jersey, USA.
Competing interests ACX was a member of the national board as a consultant for Bristol-Myers Squibb and Abbott. JW has received consulting fees from Abbott, Bristol-Myers Squibb, Shering-Plough/Essex, UCB and Wyeth. JG-R is on the advisory boards of Abbott, Bristol-Myers Squibb, Pfizer, Roche, Schering-Plough and UCB, has received lecture fees from Abbott, Bristol-Myers Squibb, Roche, Schering Plough and Wyeth, and research grants from Roche and Schering Plough. WG is a consultant for Bristol-Myers Squibb, Abbott Immunology, General Electric, Esaote and Schering-Plough, has received honoraria 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 grant/research support from 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 stock in CCBR-SYNARC. CP is owner and an employee of Spire Sciences, LLC, has stocks in Synarc, and consults for Abbott, Amgen, Biogen Idec, Celgene, Genentch, Lilly, Merck, Novartis, Roche, Servier, Simpirica and Wyeth. J-CB, DMR, ACX and RH are employees and stockholders of Bristol-Myers Squibb. RW has received consulting fees and speaker's bureau fees from Bristol-Myers Squibb, Roche, and Schering-Plough and research support from UCB. The remaining authors (JB, MR, SN, PD and S-HP) have nothing to disclose.
Patient consent Obtained.
Ethics approval The study was conducted in accordance with the Declaration of Helsinki and was consistent with International Conference on Harmonisation good clinical practice. The protocol and patient's informed consent received institutional review board/independent ethics committee approval before initiation of the study.
Provenance and peer review Not commissioned; externally peer reviewed.