A Study of RoActemra/Actemra (Tocilizumab) With or Without Methotrexate in Patients With Mild to Moderate Rheumatoid Arthritis With an Inadequate Response to Methotrexate

A Multi-center Study of the Safety and Effect on Disease Activity of Tocilizumab (TCZ) in Combination With Methotrexate (MTX) Versus Tocilizumab Monotherapy in Patients With Mild to Moderate Rheumatoid Arthritis, With Inadequate Response to MTX (Defined as DAS 28 < 4,5 and >2,6)

This multicenter study with a randomized, double-blind, parallel-group phase will evaluate the safety and efficacy of RoActemra/Actemra (tocilizumab) in combination with methotrexate versus RoActemra/Actemra monotherapy in patients with mild to moderate rheumatoid arthritis, with an inadequate response to methotrexate. Patients will receive RoActemra/Actemra 8 mg/kg intravenously every 4 weeks plus oral methotrexate 15-25 mg weekly for 12 weeks. Patients with a good/moderate EULAR response will then be randomized to receive either RoActemra/Actemra plus methotrexate or RoActemra/Actemra plus placebo for the following 12 weeks. Anticipated time on study treatment is 6 months.

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Rheumatoid arthritis of >/= 1 year duration
• Mild to moderate disease activity at screening (DAS 28 </= 4.5 and >2.6)
• On methotrexate treatment for at least 12 weeks, at stable oral dose of (10)15 mg to 25 mg/week for at least 6 weeks prior to Day 1
• Body weight </= 150 kg
• Oral corticosteroids must have been at stable dose (maximum 10 mg/day) for at least 25 out of 28 days prior to baseline

Exclusion Criteria:

• 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 rheumatoid arthritis
• Functional class IV American College of Rheumatology (ACR) Classification
• Prior history of or current inflammatory joint disease other than rheumatoid arthritis
• 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 tocilizumab
• Pregnant or lactating women
• Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
• Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections
• History of or currently active primary or secondary immunodeficiency
• Evidence of active malignant disease, malignancies diagnosed within the previous 5 years
• Active tuberculosis requiring treatment within the previous 3 years
• Positive for HIV infection