A Study to Evaluate the Safety and Efficacy of MabThera (Rituximab) in Combination With Methotrexate (MTX) in Participants With Active Rheumatoid Arthritis Who Failed on Anti-Tumor Necrosis Factor Alpha Therapy

Inclusion Criteria:

- Adult participants 18-80 years of age with active RA for at least 6 months;

- Received treatment for RA on an outpatient basis and experienced an inadequate
response or intolerance to treatment with at least 1 anti-TNF alpha therapy
(etanercept, infliximab or adalimumab);

- Must have received MTX for a minimum of 12 weeks, with the last 4 weeks, prior to
screening at a stable dose;

- Participants with swollen joint count (SJC) and tender joint count (TJC) of at least
8 joints at screening and at randomization;

- Radiographic evidence of at least 1 joint with a definite erosion due to RA;

- Participants of reproductive potential must be using reliable contraceptive methods.

Exclusion Criteria:

- Bone or joint surgery within 8 weeks prior to screening or joint surgery planned
within 24 weeks of randomization;

- Class IV functional status of RA;

- Previous treatment within 6 months with intravenous gamma globulin, or the Prosorba
column;

- Intraarticular or parenteral corticosteroids within 4 weeks prior to screening visit;

- With a live vaccine within 4 weeks prior to randomization;

- Previous treatment with rituximab or other cell-depleting therapies;

- Concurrent treatment with any disease-modifying anti-rheumatic drug (except for MTX)
or any anti-TNF alfa factor or other biologic therapy;

- History of severe allergic or anaphylactic reactions to humanized or murine
monoclonal antibodies;

- Evidence of significant uncontrolled concomitant diseases such as cardiovascular
disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal
disorders;

- Known contraindications to receiving rituximab;

- Known active bacterial, viral, fungal, mycobacterial or other infection;

- History of recurrent significant infection or history of recurrent bacterial
infections;

- Primary or secondary immunodeficiency (history of, or currently active);

- 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);

- Women who are pregnant or breast-feeding;

- History of alcohol, drug or chemical abuse within 6 months prior to screening;

- Neuropathies and neurovasculopathies which might interfere with pain evaluation;

- Participants with poor peripheral venous access;

- Intolerance or contraindications to oral or intravenous corticosteroids.