The purpose of this study is to determine if MDX-1342 given in combination with Methotrexate is a safe treatment for patients with active rheumatoid arthritis. In addition, changes in the severity patients' arthritis will also be analysed.

Inclusion Criteria:

• Must have met ACR criteria for the diagnosis of rheumatoid arthritis (RA)
• Must have active RA
• Must be treated with Methotrexate (MTX) (10 to 25 mg weekly) for at least 3 months and have received a stable dose for at least 28 days prior to the anticipated study drug administration date.
• All other DMARDs or biologics must be discontinued at least 28 days prior to study drug administration and: 1) Leflunomide, which must be discontinued at least 60 days before study drug administration, 2) infliximab, adalimumab, and abatacept must be discontinued at least 56 days prior to study drug administration

Exclusion Criteria:

• Both Rheumatoid factor and anti-CCP negative
• Prior treatment with any B-cell depleting therapy
• Any other mAb or Ig-based fusion proteins 56 days or less prior to Visit
• History of or current inflammatory joint disease other than RA
• Neuropathies or neurovasculopathies that might interfere with pain evaluation
• Complications of RA or other disease
• Any other autoimmune disease other than RA
• Acute or chronic infection
• Clinically significant disease requiring