The purpose of this study is to determine, if a weekly subcutaneous (SC) doses of abatacept will yield comparable clinical efficacy to monthly intravenous (IV) doses of abatacept in subjects with rheumatoid arthritis having an inadequate response to their current methotrexate (MTX) therapy

• Drug: Abatacept subcutaneous + placebo IV
  solution in pre-filled syringes, subcutaneous injection (+ IV infusion), 125 mg/kg in the subcutaneous injection, weekly injections, 169 days in short term; long term is open
  Other Names:

  • Orencia
  • BMS-188667
• Drug: Abatacept IV + placebo subcutaneous

  solution for IV infusion, IV infusion + subcutaneous injection, monthly IV infusions are dosed weight-tiered:

  500mg (for body weight up to 60 kg)

  750 mg (body weight between 61 and 100 kg)

  1g (body weight above 100 kg)infusions

  Other Names:

  • Orencia
  • BMS-188667

• A: Active Comparator
  double-dummy design
  Intervention: Drug: Abatacept subcutaneous + placebo IV
• B: Active Comparator
  Intervention: Drug: Abatacept IV + placebo subcutaneous

Inclusion Criteria:

• Subjects who are considered methotrexate inadequate responders
• 10 or more swollen joints (66 joint count) and 12 or more tender joints (68 joint count)

Exclusion Criteria:

• Subjects who failed one or multiple anti-TNF therapies
• Subjects who meet diagnostic criteria for any other rheumatic disease (eg, lupus erythematous)
• Subjects with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules)
• Subjects with severe chronic or recurrent bacterial infections
• Subjects who have received treatment with rituximab

Anti-TNF failure substudy at selected sites: The same criteria apply except for the exclusion of subjects who failed an anti-TNF therapy before