A Study to Assess the Effect of Tocilizumab + Methotrexate on Prevention of Structural Joint Damage in Patients With Moderate to Severe Active Rheumatoid Arthritis

• Percentage of Patients With ACR50 Response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  The ACR50 responses require a 50% improvement relative to baseline for the same criteria as ACR20 (primary outcome measure)
• Percentage of Patients With ACR70 Response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  The ACR70 responses require a 70% improvement relative to baseline for the same criteria as ACR20 (primary outcome measure)
• Swollen Joint Count (66 Joint Count): Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  66 joints are assessed for swelling and joints are classified as swollen/not swollen giving a total swollen joint count score out of 66.
• Tender Joint Count (68 Joint Count): Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total tender joint count score out of 68
• Patient's Global Visual Analog Scale (VAS): Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  The patient's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity).
• Physician's Global VAS: Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity).
• Patient's Pain VAS: Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  The patient's assessment of pain is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain".
• C-Reactive Protein (CRP): Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  The serum concentration of C-Reactive Protein (CRP) is measured in mg/dL. A reduction in the level is considered an improvement.
• Erythrocyte Sedimentation Rate: Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  The Erythrocyte Sedimentation Rate (ESR) will be measured in mm/hr. A reduction in the level is considered an improvement.
• Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  HAQ-DI is a self-completed pt questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 poss. responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. Calculate HAQ-DI the pt must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score(in range 6-8). Total poss. minimum/maximum 0-8.

This 3-arm study compared the safety and efficacy, with respect to prevention of joint damage, of tocilizumab versus placebo in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis. Patients were randomized to receive tocilizumab 4 mg intravenously (IV), tocilizumab 8 mg IV, or placebo IV, every 4 weeks. All patients also received methotrexate, 10-25 mg/week. The anticipated time on study treatment was 1-2 years and the target sample size was 500+ individuals.

• Drug: Tocilizumab
  Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly
• Drug: Tocilizumab
  Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly
• Drug: Placebo
  Placebo intravenously (IV) every 4 weeks
• Drug: Methotrexate
  10-25 mg weekly

• Experimental: Tocilizumab 4 mg/kg + Methotrexate
  Intervention: Drug: Tocilizumab
• Experimental: Tocilizumab 8 mg/kg + Methotrexate
  Intervention: Drug: Tocilizumab
• Placebo Comparator: Placebo + Methotrexate
  Interventions:

  • Drug: Placebo
  • Drug: Methotrexate

Inclusion Criteria:

• Adult patients at least 18 years of age with moderate to severe active RA for at least 6 months
• Inadequate response to a stable dose of MTX
• Patients of reproductive potential must be using reliable methods of contraception

Exclusion Criteria:

• Major surgery (including joint surgery) within 8 weeks before entering study, or planned surgery within 6 months after entering study
• Prior treatment failure with an anti-tumor necrosis factor agent
• Women who are pregnant or breast-feeding