title: Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes.
abstract: 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.
  
  
  BACKGROUND
  NCT00122382.
authors.affiliation: College of Physician and Surgeons, Columbia University, 630 West 168th Street, P&S 10-445, New York, NY 10023, USA. jmb2311@columbia.edu
authors.forename: J
authors.initials: J
authors.lastname: Bathon
authors.forename: M
authors.initials: M
authors.lastname: Robles
authors.forename: A C
authors.initials: AC
authors.lastname: Ximenes
authors.forename: S
authors.initials: S
authors.lastname: Nayiager
authors.forename: J
authors.initials: J
authors.lastname: Wollenhaupt
authors.forename: P
authors.initials: P
authors.lastname: Durez
authors.forename: J
authors.initials: J
authors.lastname: Gomez-Reino
authors.forename: W
authors.initials: W
authors.lastname: Grassi
authors.forename: B
authors.initials: B
authors.lastname: Haraoui
authors.forename: W
authors.initials: W
authors.lastname: Shergy
authors.forename: S-H
authors.initials: SH
authors.lastname: Park
authors.forename: H
authors.initials: H
authors.lastname: Genant
authors.forename: C
authors.initials: C
authors.lastname: Peterfy
authors.forename: J-C
authors.initials: JC
authors.lastname: Becker
authors.forename: A
authors.initials: A
authors.lastname: Covucci
authors.forename: D
authors.initials: D
authors.lastname: Moniz Reed
authors.forename: R
authors.initials: R
authors.lastname: Helfrick
authors.forename: R
authors.initials: R
authors.lastname: Westhovens
mesh_terms: D000069594:Abatacept; D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D012074:Remission Induction; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept; D008727:Methotrexate