TORPEDO Study: A Study on Rapid Effect of Tocilizumab in Patients With Rheumatoid Arthritis With an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) or Anti-TNF

• Improvement in global disease activity VAS [ Time Frame: measured daily for 4 weeks after 1st infusion, and after 3, 6 and 12 months of treatment ] [ Designated as safety issue: No ]
• Effect on synovitis score at ultrasound [ Time Frame: assessed day 7 and at month 1,3,6 and 12 ] [ Designated as safety issue: No ]
• Effect on inflammation biological parameters [ Time Frame: assessed day 7 and at month 1,3,6 and 12 ] [ Designated as safety issue: No ]
• Effect on bone density by DEXA and on bone and cartilage markers [ Time Frame: assessed day 7 and at month 1, 3 and 12 ] [ Designated as safety issue: No ]

This study will assess the onset and maintenance of effect of tocilizumab on relief in patients with active moderate or severe rheumatoid arthritis who have had an inadequate response to DMARDs or anti-TNF. For the first, double-blind, part of the study patients will be randomized to receive an iv infusion of either 8mg/kg tocilizumab or placebo. After 4 weeks this will be followed by 11 months treatment with tocilizumab 8mg/kg iv infusion every 4 weeks. Methotrexate or DMARD therapy will be continued throughout study treatment. Target sample size is >100.

• Drug: tocilizumab [RoActemra/Actemra]
  single iv infusion 8 mg/kg
• Drug: placebo
  single iv infusion
• Drug: tocilizumab [RoActemra/Actemra]
  iv infusion 8mg/kg every 4 weeks for 11 months

• Experimental: 1
  Intervention: Drug: tocilizumab [RoActemra/Actemra]
• Placebo Comparator: 2
  Intervention: Drug: placebo
• Experimental: 3
  Intervention: Drug: tocilizumab [RoActemra/Actemra]

Inclusion Criteria:

• adult patients >/= 18 years of age
• active moderate or severe rheumatoid arthritis of <10 years duration with inadequate response to methotrexate or anti-TNF
• on methotrexate treatment for at least 10 weeks, at least 8 weeks on stable dose
• patients receiving oral corticosteroids and/or NSAIDs should be at stable dose for 4 weeks

Exclusion Criteria:

• rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA
• functional class IV by ACR classification
• history of inflammatory joint disease other than RA
• previous treatment with cell-depleting therapies, abatacept or rituximab
• active current or history of recurrent infection, or any major episode of infection requiring hospitalization or treatment with iv antibiotics <4 weeks or oral antibiotics <2 weeks prior to screening