Inclusion Criteria:

Male and female patients, 18 to 75 years of age, with active rheumatoid arthritis (RA) who
have had an inadequate response to disease modifying anti-rheumatic drugs, not more than 3
non-biological DMARDs including leflunomide, and not more than one inadequate response to
anti-TNF-therapy, and currently have active disease despite at least 3-month treatment
with leflunomide. Active disease is defined as DAS 28 >3.2 and at least swollen joint
count (SJC) ≥ 3 and tender joint count (TJC) ≥ 3 included in the 28 joint count.

- Male and female patients with rheumatoid arthritis for at least 3 months diagnosed
according to the revised 1987 ACR criteria for the classification of rheumatoid
arthritis.

- Willingness and capability to give written informed consent, and willingness to
participate and to comply with the study protocol.

- Not more than 2 non-biological DMARDs other than leflunomide in history, which are
washed out at least 4 weeks prior to first rituximab infusion

- Previous use of anti-TNF therapy is allowed. Patient will only be allowed to be
pre-treated with a maximum of two anti-TNF therapies and only one stopped due to
inadequate response. The second anti-TNF could be stopped for instance due to
intolerance, e.g. injection site reactions. Anti-TNF treatment must be discontinued
prior to baseline considering the different characteristics of the specific compound:
Use of infliximab, adalimumab, certolizumab, golimumab within 8 weeks of baseline,
use of etanercept within 4 weeks of baseline.

Exclusion Criteria:

- RA functional class IV: limited in ability to perform usual self-care, work, and
other activities

- Male and female patients with other chronic inflammatory articular disease or
systemic autoimmune disease

- Any active infection, a history of recurrent clinically significant infection, a
history of recurrent bacterial infections with encapsulated organisms (Hepatitis B, C
and HIV (human immune deficiency virus) - will be tested at screening)

- Chronic, latent and acute infections of the lung

- Positive result of a Tuberculosis specific Interferon gamma release assay (will be
tested at screening)

- Primary or secondary immunodeficiency

- History of cancer with curative treatment not longer than 5 years ago except
basal-cell carcinoma of the skin that had been excised

- Evidence of significant uncontrolled concomitant diseases or serious and / or
uncontrolled diseases that are likely to interfere with the evaluation of the
patient's safety and of the study outcome

- Neuropathy that can interfere with filling out the patient's questionnaires

- History of a severe psychological illness or condition

- Known hypersensitivity to any component of the product or to murine proteins

- Severe heart failure (New York Heart Association Class III and IV) or
severe,uncontrolled cardiac disease.

- Women lactating, pregnant, nursing or of childbearing potential with a positive
pregnancy test or planned pregnancy.

- Women of childbearing potential without adequate contraception (medically acceptable
methods (pearl Index < 1) are contraceptive implant, contraceptive injection,
intrauterine device (IUD), or oral contraceptives taken for at least 3 months,which
the patient agrees to continue using during the study, or a double-barrier method
which must consist of a combination of any of the following: diaphragma,cervical cap,
condom, or spermicide)

- History of alcohol, drug or chemical abuse (defined as impaired / questionable
reliability) as well as neurotic personality.

- Participation in another investigational study within 4 weeks prior to the screening
visit.

- Previous treatment with any B-cell depleting agents including rituximab

- Intolerance to ingredients of rituximab or murine proteins

- Pre-treatment with abatacept, tocilizumab or other anti-TNF biologicals.

- Inadequate response to more than one anti-TNF-therapy

- Pre-treatment of more than two anti-TNF, only one is allowed to be stopped due to
inadequate response. The second anti-TNF could be stopped due to intolerance, e.g.
injection site reactions

- Corticosteroids at doses exceeding 10 mg per day of prednisolone or equivalents
within the last 2 weeks or corticosteroids at instable doses within the last 2 weeks

- Intolerance or contraindication to drugs required for the treatment of the side
effects of rituximab

- Previous treatment with any investigational medicinal product within last 3 months
prior to baseline

- Receipt of a live vaccine within 4 weeks prior to treatment

- Intra- articular or parenteral corticosteroids within 4 weeks prior to screening
visit

- Haemoglobin < 8.5 g / dl (equivalent to < 5,28 mmol/l Haemoglobin)

- Neutrophil counts < 1.500 / μl (equivalent to 1,5 / nl)

- Platelet count < 75.000 / μl (equivalent to 75 / nl)

- Lower than 500 / μl (equivalent to 0,5 / nl) lymphocytes

- Serum creatinine > 1.4 mg / dl for women or 1.6 mg / dl for men

- Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 2.5 times upper
limit of normal

- IgG (immunoglobulin G) level < 5g/l