A Study of Tocilizumab and Methotrexate Treatment Strategies (Adding Tocilizumab to Methotrexate Versus Switching to Tocilizumab) in Patients With Active Rheumatoid Arthritis With Inadequate Response to Prior Methotrexate Treatment

• Inhibition of progressive joint damage [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
• ACR20/50/70/90 response, and time to response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
• DAS, DAS28, HAQ [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

This 2 arm study will compare 2 treatment strategies based on tocilizumab and/or methotrexate in patients with moderate to severe rheumatoid arthritis. Patients receiving methotrexate treatment will be randomized to receive either a)tocilizumab 8mg iv every 4 weeks + methotrexate po weekly or b)tocilizumab 8mg iv every 4 weeks + placebo po weekly. After the first 24 weeks of blinded treatment, treatment adjustments (increase or decrease of treatment intensity) may be introduced at intervals, based on response. The anticipated time on study treatment is 2 years, and the target sample size is 100-500 individuals.

• Drug: tocilizumab [RoActemra/Actemra]
  8mg iv every 4 weeks
• Drug: methotrexate
  >15mg po weekly
• Drug: placebo
  po weekly

• Experimental: 1
  Interventions:

  • Drug: tocilizumab [RoActemra/Actemra]
  • Drug: methotrexate
• Placebo Comparator: 2
  Interventions:

  • Drug: tocilizumab [RoActemra/Actemra]
  • Drug: placebo

Inclusion Criteria:

• adult patients, >=18 years of age;
• moderate to severe active rheumatoid arthritis (DAS28 >4.4);
• inadequate response to methotrexate;
• on a stable dose of >=15mg/week methotrexate for at least 6 weeks.

Exclusion Criteria:

• prior treatment with a biologic;
• RA functional class IV;
• known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections;
• evidence of active malignant disease.