• Compare the clinical efficacy of BMS-188667 used in combination with methotrexate versus methotrexate alone on: Symptomatic relief as measured by ACR20 following 6 months of treatment [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
• Compare the clinical efficacy of BMS-188667 used in combination with methotrexate versus methotrexate alone on: Physical function as measured by the disability index of the HAQ at 12 months [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
• Compare the clinical efficacy of BMS-188667 used in combination with methotrexate versus methotrexate alone on: Structural damage as assessed by erosion scores using a Genant-modified method at 12 months of treatment [ Time Frame: Day 365 ] [ Designated as safety issue: Yes ]
• The primary objective of long term extension is to assess the safety and long term tolerability of BMS-188667 in subjects who have completed the initial 12-month double-blind treatment period [ Time Frame: Long term extension ] [ Designated as safety issue: Yes ]

• Determine the effect of BMS-188667 in combination with methotrexate on structural damage as assessed by total and joint space narrowing score using a Genant-modified Sharp method at 12 months of treatment [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
• Compare ACR 50 and ACR 70 [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
• Assessed ACR 20, ACR 50, and ACR 70 [ Time Frame: Over time ] [ Designated as safety issue: No ]
• Determine the proportion of subjects receiving BMS-188667 in combination with methotrexate who achieve a major clinical response (continuous ACR 70) [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
• Assess disease activity as measured by Disease Activity Score-28 (DAS-28) [ Time Frame: Day 1, Day 169, and Day 365 ] [ Designated as safety issue: No ]
• Assess the safety of chronic use of BMS-188667 in combination with methotrexate [ Time Frame: every 28 months ] [ Designated as safety issue: No ]
• Assess the discontinuation rate in subjects receiving BMS-188667 in combination with methotrexate [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
• Assess the incidence of new tender and swollen joints and 100% reduction in joint counts [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
• Assess the immunogenicity of BMS-188667 in combination with methotrexate [ Time Frame: Day 1, Day 169, and Day 365 ] [ Designated as safety issue: No ]
• Assess changes of surrogate markers (RF, CRP, ESR, IL2-r) in subjects receiving BMS-188667 in combination with methotrexate [ Time Frame: Day 169 ] [ Designated as safety issue: Yes ]
• Assess the changes of functional status as measured by the disability index and individual components of the HAQ in subjects receiving BMS-188667 in combination with methotrexate [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
• Assess the change of subject's health-related quality of life, as measured by the SF-36 questionnaire in subjects receiving BMS-188667 in combination with methotrexate [ Time Frame: Day 1, Day 29, Day 85, Day 169 ] [ Designated as safety issue: No ]
• Assess the pharmacokinetics of BMS-188667 [ Time Frame: Day 1-Day 169, Day 225, Day 281, Day 337 ] [ Designated as safety issue: Yes ]
• Determine the effect of BMS-188667 in combination with methotrexate on structural damage as assessed by x-ray evaluation in subjects with RA after two years of treatment [ Time Frame: Day 729 ] [ Designated as safety issue: Yes ]
• Assess chx of functional status measured by disability index & individual components of HAQ in subjects receiving BMS-188667 in combination with methotrexate to determine if any improvement in HAQ associated with BMS-188667 treatment - long-term adm [ Time Frame: Day 365 and over time ] [ Designated as safety issue: No ]
• Assess ACR 20, ACR 50, and ACR 70 [ Time Frame: over time ] [ Designated as safety issue: No ]
• Determine the proportion of subjects receiving BMS-188667 in combination with methotrexate who achieve a major clinical response (continuous ACR 70 for six months) [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
• Assess disease activity as measured by Disease Activity Score-28 (DAS-28), at each quarterly visit [ Time Frame: every 3 months ] [ Designated as safety issue: Yes ]
• Assess the immunogenicity of BMS-188667 in combination with methotrexate [ Time Frame: every 6 months ] [ Designated as safety issue: Yes ]
• Assess changes of surrogate markers (RF, CRP, ESR, IL-6, MMP-3) in subjects receiving BMS-188667 in combination with methotrexate [ Time Frame: CRP & ESR-every 3 months; all other tests - every 6 months ] [ Designated as safety issue: Yes ]
• Assess the change of subject's health-related quality of life, as measured by the SF-36 questionnaire in subjects receiving BMS-188667 in combination with methotrexate [ Time Frame: every 6 months ] [ Designated as safety issue: No ]

Short Term: The purpose of this clinical research study is to learn if BMS-188667 in combination with methotrexate is better than methotrexate alone in subjects that have active rheumatoid arthritis and are not responding to methotrexate. The safety of this treatment will also be studied.

Long Term Extension: The purpose of this amendment is to provide subjects who have completed the initial 12-month double-blind treatment period the opportunity to receive open label treatment with active drug treatment until BMS-188667 is approved in the local country or until clinical development has been discontinued.

• Drug: BMS-188667
• Drug: Methotrexate
• Drug: Placebo

• Experimental: Short Term
• Placebo Comparator: Short Term
• Other:

  Open Label

  Long Term Extension

• Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechinski J, Li T, Ge Z, Becker JC, Westhovens R. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2006 Jun 20;144(12):865-76. Summary for patients in: Ann Intern Med. 2006 Jun 20;144(12):I18.
• Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechiński J, Li T, Teng J, Becker JC, Westhovens R. Results of a two-year followup study of patients with rheumatoid arthritis who received a combination of abatacept and methotrexate. Arthritis Rheum. 2008 Apr;58(4):953-63.

• Rheumatoid Arthritis for greater than 1 year from the time of initial diagnosis of RA.
• Patients must have been taking methotrexate for at least 3 months with at least a weekly dose of 15 mg.