A Study of RoActemra/Actemra (Tocilizumab) Versus Adalimumab in Combination With Methotrexate in Patients With Moderate to Severe Active Rheumatoid Arthritis And an Inadequate Response to Treatment With Only One TNF-Inhibitor

• Efficacy according to American College of Rheumatology (ACR) criteria [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Efficacy according to European League Against Rheumatism (EULAR) criteria [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Proportion of patients achieving low disease activity (DAS28 <3.2) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Quality of life: Health Assessment Questionnaire (HAQ) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Quality of life: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Quality of life: Short-Form-36 (SF-36) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Quality of life: Routine Assessment of Patient Index Data (RAPID3) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Change in hemoglobin levels [ Time Frame: from baseline to Week 24 ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]

This randomized, parallel-group study will assess the efficacy and safety of RoActemra/Actemra (tocilizumab) versus adalimumab in combination with methotrexate in patients with moderate to severe active rheumatoid arthritis. Patients will be randomized to receive either RoActemra/Actemra 8 mg/kg intravenously (iv) every 4 weeks or adalimumab 40 mg sc every 2 weeks. All patients will receive methotrexate (10-25 mg weekly) and folate (at least 5 mg weekly). The anticipated time on study treatment is 24 weeks.

• Drug: tocilizumab [RoActemra/Actemra]
  8 mg/kg iv every 4 weeks, 24 weeks
• Drug: adalimumab
  40 mg sc every 2 weeks, 24 weeks
• Drug: Placebo
  tocilizumab placebo iv every 4 weeks, 24 weeks
• Drug: Placebo
  adalimumab-placebo sc every 2 weeks, 24 weeks
• Drug: methotrexate
  10-25 mg weekly
• Drug: folate
  >/= 5 mg weekly

• Experimental: A
  Interventions:

  • Drug: tocilizumab [RoActemra/Actemra]
  • Drug: Placebo
  • Drug: methotrexate
  • Drug: folate
• Active Comparator: B
  Interventions:

  • Drug: adalimumab
  • Drug: Placebo
  • Drug: methotrexate
  • Drug: folate

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Rheumatoid arthritis of >/= 6 months duration (according to ACR criteria)
• Inadequate response due to inefficacy of treatment (for at least 3 months) with only one approved TNF-agent other than adalimumab. Depending on the TNF-inhibitor, last dose of TNF-inhibitor should have been 1 to 8 weeks before randomization to the study
• On methotrexate treatment for >/=12 weeks immediately prior to baseline, with stable dose (10-25 mg/week) for the last 8 weeks
• Disease Activity Score (DAS28) >3.2 at baseline
• Oral corticosteroids (</=10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs) are permitted if the dose has been stable for >/=6 weeks prior to baseline

Exclusion Criteria:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 6 months following randomization
• Rheumatic autoimmune disease other than rheumatoid arthritis
• Prior history of or current inflammatory joint disease other than rheumatoid arthritis
• Functional class IV (ACR criteria)
• History of severe allergic reaction to human, humanized or murine monoclonal antibodies
• Known active current or history of recurrent infection (including tuberculosis)
• Primary or secondary immunodeficiency (history of or currently active)
• Body weight >150 kg
• Previous treatment with any cell-depleting therapies
• Previous treatment with tocilizumab
• Intra-articular or parenteral corticosteroids within 6 weeks prior to baseline