Inclusion Criteria:

1. Able and willing to give written informed consent and comply with the requirements of the study protocol.
2. Patients with rheumatoid arthritis for at least 6 months, diagnosed according to the revised 1987 ACR criteria for the classification of rheumatoid arthritis.
3. Receiving treatment on an outpatient basis.
4. Experienced an inadequate response to previous or current treatment with etanercept, infliximab or adalimumab because of toxicity or inadequate efficacy (etanercept for ≥ 3 months at 25 mg twice a week, at least 4 infusions of infliximab at ≥ 3 mg/kg or adalimumab for ≥ 3 months at 40 mg every other week).
5. Washed out from etanercept for ≥ 4 weeks and infliximab or adalimumab for ≥ 8 weeks prior to randomization.
6. Must have received MTX at a dose 10-25 mg/week (p.o. or parenteral) for at least 12 weeks, with the last 4 weeks, prior to screening at a stable dose.
7. All DMARDs other than MTX should be withdrawn at least 4 weeks prior to randomization (8 weeks for infliximab, leflunomide and adalimumab).
8. Swollen joint count (SJC) ≥ 8 (66 joint count), and tender joint count (TJC) ≥ 8(68 joint count) at screening and randomization.
9. At screening, either CRP ≥ 1.5 mg/dL (15 mg/L) OR ESR ≥ 28 mm/h
10. Radiographic evidence of at least one joint with a definite erosion attributable to rheumatoid arthritis, as determined by the central reading site. Any joint of the hands, wrists or feet can be considered with the exception of the DIP joints of the hands.
11. Age 18-80 years.
12. Corticosteroids (≤ 10 mg/day prednisone or equivalent) permitted if stable for at least 4 weeks prior to screening and NSAIDs permitted if stable for at least 2 weeks prior to screening.
13. Patients of reproductive potential (males and females) using a reliable means of contraception (e.g. contraceptive pill, IUD, physical barrier).
14. Must be willing to receive oral folate.
15. If female and of childbearing potential, a negative urine pregnancy test within two weeks prior to randomization (or Rescue Therapy).

Exclusion Criteria:

1. Bone/joint surgery within 8 weeks prior to screening (including joint fusion), or joint surgery planned within 24 weeks of randomization.
2. Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Sjogren's syndrome with RA is permitted.
3. Functional class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis.
4. History of, or current, inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic rheumatic disorder (e.g., SLE, inflammatory bowel disease, scleroderma, inflammatory myopathy, overlap syndrome).

Excluded Previous/Concomitant Medications:

1. Concurrent treatment with any DMARD (apart from methotrexate), or any anti-TNF-α therapy or other biologic therapy.
2. Treatment with any investigational agent within 4 weeks of screening or 5 half lives of the investigational drug (whichever is the longer).
3. Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19).
4. Previous treatment within 6 months with intravenous gamma globulin, or the Prosorba Column.
5. Intraarticular or parenteral corticosteroids within 4 weeks prior to screening visit
6. Immunization with a live vaccine within 4 weeks prior to randomization.
7. Previous treatment with rituximab (MabThera/Rituxan).

Exclusions for General Safety:

1. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
2. Significant cardiac or pulmonary disease (including obstructive pulmonary disease).
3. Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders.
4. Known active bacterial, viral, fungal, mycobacterial or other infection (including tuberculosis, or atypical mycobacterial disease, but excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening.
5. History of recurrent significant infection or history of recurrent bacterial infections.
6. Primary or secondary immunodeficiency (history of, or currently active).
7. History of cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that have been excised and cured).
8. Pregnant women or nursing (breast feeding) mothers.
9. History of alcohol, drug or chemical abuse within 6 months prior to screening.
10. Neuropathies and neurovasculopathies which might interfere with pain evaluation.
11. Patients with poor peripheral venous access.
12. Intolerance or contraindications to p.o. or i.v. corticosteroids.

Laboratory Exclusion Criteria (at Screening):

1. Serum creatinine > 1.4 mg/dL for women or 1.6 mg/dL for men.
2. AST or ALT > 2.5 times upper limit of normal.
3. Platelet count < 100,000/µL.
4. Hemoglobin < 8.5 g/dL.
5. Neutrophils < 1.5 × 103/µL.
6. Positive tests for hepatitis B surface antigen or hepatitis C antibody.
7. Levels of IgG and/or IgM below 5.65 and 0.55 mg/mL respectively.