This single arm study will evaluate the safety and efficacy of MabThera in participants with active rheumatoid arthritis who have had an inadequate response to prior treatment with DMARDs and/or anti-TNF alpha agent. Participants will be treated with MabThera 1000 milligrams (mg) intravenously (IV) on days 1 and 15. Participants were followed every 8 weeks to complete 24 weeks of follow-up. After completion of the Week 24 visit, the participants were followed every 3 months for up to 18 months for an overall study duration of 24 months (104 weeks). After week 36, eligible participants who achieve moderate or good response according to the European League Against Rheumatism (EULAR) response criteria will receive re-treatment with MabThera. Participants will receive concomitant treatment with DMARDs, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics throughout the study period. The anticipated time on study treatment is 2 years, and the target sample size is 200 participants.

Inclusion Criteria:

During study entry

• Able and willing to give written informed consent and comply with the requirements of the study protocol;
• Participants with Rheumatoid Arthritis (RA) for at least 6 months, diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of RA;
• Receiving treatment on an outpatient basis;
• Experienced an inadequate response to previous or current treatment with DMARDs because of toxicity or inadequate efficacy;
• Disease activity score (DAS28) greater than or equal to (>=) 3.2 at screening and baseline visit.
• Age >= 18 years;
• Participants of reproductive potential (males and females) using a reliable means of contraception (for example [e.g.] contraceptive pill, intrauterine device, physical barrier);
• Female participants with childbearing potential - a negative urine pregnancy test within two weeks prior to first rituximab treatment.

During Re-Treatment

• Achieved moderate or good response according to the EULAR response criteria during any visit including visits in the post-treatment period;
• DAS28 >=3.2;
• The participants has not been withdrawn into the safety follow-up at any time pre or post Week 24;
• 36 weeks or more have passed since the participant's first rituximab infusion;
• No evidence of any new medical condition or laboratory test results;
• In participants who were known to be positive to hepatitis B core antibody (HBcAb) - documented negative hepatitis B viral DNA (HBV-DNA) test and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than or equal to (<=) 2.5x upper limit of normal (ULN) within the last 12 weeks;
• Female participants with childbearing potential - a negative urine pregnancy test immediately prior to treatment initiation.

Exclusion Criteria:

• 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 was permitted;
• Functional class IV as defined by the ACR Classification of Functional Status in RA;
• 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 disorder (e.g., inflammatory bowel disease, scleroderma, inflammatory myopathy);

Excluded Previous/Concomitant Medications

• Previous or concurrent treatment with any anti TNF-alpha therapy;
• Treatment with any investigational agent within 4 weeks of screening;
• Previous treatment with any cell depleting therapies excluding rituximab, including investigational agents;
• Immunization with a live vaccine within 4 weeks prior to the baseline visit.

Exclusions for General Safety

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies;
• Significant cardiac or pulmonary disease (including obstructive pulmonary disease).
• Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders.
• 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;
• History of recurrent significant infection or history of recurrent bacterial infections;
• Primary or secondary immunodeficiency (history of, or currently active);
• Active cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that have been excised and cured);
• Pregnant women or nursing (breast feeding) mothers;
• Participants with lack of peripheral venous access;

Laboratory Exclusion Criteria (at Screening)

• Positive tests for hepatitis B surface antigen (HBsAg) and/or positive tests for HBcAb associated with detectable HBV-DNA or hepatitis C antibody (HCAb) and hepatitis C viral RNA (HCV-RNA).