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

• The primary endpoint fo the trial is change in 1.5 Tesla MRI erosion score (RAMRIS system) from baseline to Week 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  

• Change from Baseline in 1.5 Tesla MRI synovitis score (RAMRIS system) at Week 12. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  
• Change from Baseline in 1.5 Tesla MRI bone edema and total score (RAMRIS system) at Week 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  
• Change from Baseline in 1.5 Tesla MRI bone edema, bone erosion and total score (RAMRIS system) at Week 12 and Week 48. [ Time Frame: 12 and 48 weeks ] [ Designated as safety issue: No ]
  
• Proportion of patients at Week 48 without new bone erosions on 1.5 Tesla MRI. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  
• Change from baseline in total Genant modified Sharp score on conventional radiographs at Week 24 and 48. [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  
• Change in Disease Activity Score (DAS 28) from Baseline to Week 24 and 48. [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  
• ACR remission and responder rates (20%, 50%, &)%) at Week 24 and 48. [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  
• Change from Baseline in functional assessments according to the HAQ scores at 24 and 48 Weeks. [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  
• Difference between relative results from conventional high-field strength 1.5 Tesla MRI and 0.2 Tesla dedicated extremity MRI in detection and grading of bone erosions, bone edema, and synovitis at Baseline and in Week 12,24, and 48 (C-scan validation). [ Time Frame: 12, 24 and 48 weeks ] [ Designated as safety issue: No ]
  

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.