Impact of Rituximab on MRI Evidence of Disease Activity in Patients With Moderate to Severe Rheumatoid Arthritis

Rituximab is a monoclonal antibody that has been approved for the treatment of non-Hodgkin's
B cell lymphoma (a type of cancer) and for certain patients with rheumatoid arthritis (RA)
by the Food and Drug Administration (FDA). To date, more than 1000 subjects with rheumatoid
arthritis have received rituximab in clinical studies.

Magnetic resonance imaging (MRI) is a modern and sensitive method of looking at joints in
people with rheumatoid arthritis. It uses a magnetic field to create an image. The MRI
takes an image in 3 dimensions and this provides a better picture for a physician to see
more details.

There are two treatment groups in this study with equal numbers of patients assigned to
each group. All the patients will receive their baseline Methotrexate and two intravenous
infusions 2 weeks apart of one of the following:

- 1000 mg rituximab or

- placebo. Patients outcomes will be compared between the 2 groups. After week 24 (open
label phase), the patients will receive rituximab if rheumatoid arthritis remains
active.

All the patients will have MRI of their dominant hand and wrist with and without gadolinium
performed at baseline, 12, 24 and 48 weeks on 1.5 Tesla MRI . Some patients will also have
additional MRI of the same hand and wrist without gadolinium at the same time points on 0.2
Tesla MRI. Comparison of the images from the two machines will be performed.

Various blood biomarkers will also be examined, compared between the 2 treatment groups and
correlated with the MRI results.