A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate Versus RoActemra/Actemra Monotherapy in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate

A Multi-center Study of the Safety and Effect on Disease Activity of Tocilizumab (TCZ) in Combination With MTX Versus Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis, With Inadequate Response to MTX (Defined as DAS 28 > 3,2)

This randomized, double-blind, parallel-group study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in combination with methotrexate versus RoActemra/Actemra monotherapy in patients with rheumatoid arthritis and an inadequate response to methotrexate. All patients will receive RoActemra/Actemra 8 mg/kg intravenously (iv) every 4 weeks plus oral methotrexate for 16 weeks. Patients achieving low disease activity at Week 16 will be randomized to receive a further 12 weeks of RoActemra/Actemra treatment plus either methotrexate or placebo. Anticipated time on study treatment is 28 weeks.

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Active moderate to severe rheumatoid arthritis (DAS28 >/= 3.2) at baseline
• Currently receiving methotrexate for at least 12 weeks, at a stable oral dose of at least 15 mg/week for at least 6 weeks prior to treatment (Day 1)
• Body weight < 150 kg
• Oral corticoids must have been at stable dose for at least 25 out of 28 days prior to baseline; maximum dose 10 mg/day

Exclusion Criteria:

• Pregnant or nursing women
• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after baseline
• Rheumatic autoimmune disease other than RA
• Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis
• Prior history of or current inflammatory joint disease other than RA
• Treatment with a biologic agent at any time prior to baseline
• Treatment with traditional DMARDs other than methotrexate within 1 month (for leflunomide 3 months) prior to baseline
• Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
• Previous treatment with RoActemra/Actemra
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
• Known active current or history of recurrent infection
• History of or currently active primary or secondary immunodeficiency
• Active tuberculosis requiring treatment within the previous 3 years
• Positive for HIV infection