A Study of Subcutaneously Administered Tocilizumab in Patients With Rheumatoid Arthritis

Open-label, Multicenter, Randomized, Parallel Study to Investigate pk, pd, Efficacy and Safety of Tocilizumab (TCZ, RO4877533) Following Subcutaneous Administration of TCZ 162 mg Weekly or Every Other Week in Combination With Methotrexate in Patients With Rheumatoid Arthritis

This open-label randomized 2arm study will investigate the pharmacokinetics, pharmacodynamics, efficacy and safety of subcutaneously administered tocilizumab in patients with rheumatoid arthritis who have shown an inadequate response to methotrexate. Patients will be randomized to receive tocilizumab 162 mg sc either weekly or every other week, in combination with methotrexate, for 12 weeks. Assessments will be made at regular intervals during treatment and on the 3 weeks of follow-up.Target sample size is < 50 individuals.

Inclusion Criteria:

• adults 18 - 75 years of age
• active rheumatoid arthritis of >/= 6 months duration
• inadequate response to at least 12 weeks of methotrexate, the last 8 prior to baseline on stable dose
• swollen joint count (SJC)>/=4, tender joint count (TJC)>/=6 at screening and baseline
• DMARDs and anti-TNFs, other than methotrexate, withdrawn prior to baseline
• oral corticosteroids (</= 10mg/day prednisone or equivalent) and NSAIDS on stable dose </= 4 weeks prior to baseline

Exclusion Criteria:

• rheumatic autoimmune disease other than rheumatoid arthritis
• prior history or current inflammatory joint disease other than rheumatoid arthritis
• major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following enrollment
• functional class IV by ACR classification