This 3-part study will evaluate the efficacy and safety of tocilizumab in patients with active polyarticular-course juvenile idiopathic arthritis who have an inadequate response to, or were intolerant of methotrexate. In Part I of the study all patients will receive iv infusions of tocilizumab (8mg/kg for patients >/=30kg, 8mg/kg or 10mg/kg for patients <30kg) every 4 weeks for 16 weeks. For Part II, patients with an adequate response in Part I will be randomized to receive either tocilizumab at the same dose as in Part I or placebo, every 4 weeks for up to 24 weeks. In Part III of the study patients will receive tocilizumab at the same dose as in Part I every 4 weeks for up to another 64 weeks. Standard of care therapy with or without NSAIDs, corticosteroids or methotrexate will continue throughout the study. Anticipated time on study treatment is 2 years, and target sample size is 150-200 individuals.

• Drug: tocilizumab
  8mg/kg or 10mg/kg iv infusion every 4 weeks, 16 weeks
• Drug: tocilizumab
  8mg/kg or 10mg/kg iv infusion every 4 weeks, 24 weeks
• Drug: tocilizumab
  8mg/kg or 10 mg/kg iv infusion every 4 weeks, 64 weeks
• Drug: placebo
  iv infusion every 4 weeks, 24 weeks
• Drug: NSAIDs, corticosteroids, methotrexate
  as prescribed

• I: Active Comparator
  Interventions:

  • Drug: tocilizumab
  • Drug: NSAIDs, corticosteroids, methotrexate
• IIA: Experimental
  Interventions:

  • Drug: tocilizumab
  • Drug: NSAIDs, corticosteroids, methotrexate
• IIB: Placebo Comparator
  Interventions:

  • Drug: placebo
  • Drug: NSAIDs, corticosteroids, methotrexate
• III: Active Comparator
  Interventions:

  • Drug: tocilizumab
  • Drug: NSAIDs, corticosteroids, methotrexate

Inclusion Criteria:

• children/juveniles, 2-17 years of age
• polyarticular-course juvenile idiopathic arthritis (pcJIA) >/=6 months duration
• active disease (>/=5 active joints, >/=3 with limitation of motion)
• inadequate response to or inability to tolerate methotrexate
• methotrexate, oral corticosteroids and NSAIDs at stable dose(at least 8,4 and 2 weeks,respectively) prior to baseline
• biologics discontinued, between at least 1 and 20 weeks prior to baseline, depending on biologic

Exclusion Criteria:

• auto-immune, rheumatic disease or overlap syndrome other than polyarticular-course JIA
• wheelchair bound or bedridden
• intraarticular, intramuscular, intravenous or long-acting corticosteroids within 4 weeks prior to baseline
• DMARDs (other than methotrexate) within 4 weeks prior to baseline
• previous treatment with tocilizumab