A Study of MabThera (Rituximab) in Participants With Rheumatoid Arthritis Who Have Had an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARD) and/or Anti-Tumor Necrosis Factor (Anti-TNF) Therapy.
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Rituximab [MabThera/Rituxan]
Intervention description: 1000 mg IV on days 1 and 15
Intervention MeSH terms: Rituximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 215.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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).