A Study of Tocilizumab in Comparison to Etanercept in Participants With Rheumatoid Arthritis and Cardiovascular Disease Risk Factors
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Etanercept; Tocilizumab
Intervention description: Participants will receive 50 mg etanercept subcutaneously weekly until switch to another RA therapy or up to 4.9 years.; Participants will receive 8 mg/kg tocilizumab IV every 4 weeks until switch to another RA therapy or up to 4.9 years.
Intervention MeSH terms: Etanercept
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3080.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No

Summary:

      This randomized, open-label, parallel-group, multicenter study will evaluate the rate of
      cardiovascular events with tocilizumab in comparison to etanercept in participants with
      rheumatoid arthritis (RA). Participants will be randomized to receive intravenous (IV) 8
      milligrams per kilogram (mg/kg) tocilizumab every 4 weeks or subcutaneous 50 milligrams (mg)
      etanercept weekly, with or without non-biologic disease-modifying anti-rheumatic drug
      (DMARD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants with moderate to severe RA of greater than or equal to (>=6) months
             duration

          -  Inadequate response to at least one non-biologic DMARD

          -  Positive for Rheumatoid Factor (RF) and/or anti-cyclic citrullinated peptide (CCP)
             antibodies at screening

          -  Have C-reactive protein (CRP) greater than (>) 0.3 milligrams per deciliter (mg/dL) at
             screening or at the baseline visit

          -  Swollen joint count (SJC) >=8 (66 joint count) and tender joint count (TJC) >= 8 (68
             joint count) during screening or at the baseline visit

          -  History of Coronary Heart Disease (CHD) or presence of one or more additional CHD risk
             factors, including current cigarette smoking, hypertension, low High Density
             Lipoprotein (HDL) cholesterol, family history of premature CHD, diabetes, presence of
             extra-articular disease associated with rheumatoid arthritis

          -  At the time of randomization, will have discontinued infliximab, adalimumab,
             golimumab, or certolizumab for >= 4 weeks

        Exclusion Criteria:

          -  Major surgery (including joint surgery or coronary revascularization) within 8 weeks
             prior to screening or planned major surgery within 1 year of study start

          -  Rheumatic autoimmune disease other than RA

          -  History of or current inflammatory joint disease other than RA

          -  Current or recent (within past 3 months) evidence of serious uncontrolled concomitant
             cardiovascular or cerebrovascular disease (myocardial infarction, revascularization,
             stroke, transient ischemic attack, or acute coronary syndrome)

          -  Current or previous (within the past 2 years) evidence of serious uncontrolled
             concomitant pulmonary (including obstructive pulmonary disease), renal, hepatic,
             endocrine (including uncontrolled diabetes mellitus) or gastrointestinal disease

          -  Uncontrolled disease states, such as asthma or inflammatory bowel disease where flares
             are commonly treated with oral or parenteral corticosteroids

          -  Pre-existing central nervous system demyelinating or seizure disorders

          -  History of diverticulitis, diverticulosis requiring treatment or other lower
             gastrointestinal tract conditions that might predispose to perforations

          -  Current liver disease as determined by the investigator; a history of asymptomatic
             elevations in liver function tests (LFTs) is not considered an exclusion

          -  Active current infection or history of recurrent bacterial, viral, fungal,
             mycobacterial or other infections, including but not limited to tuberculosis and
             atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding
             fungal infections of nail beds

          -  Any major episode of infection requiring hospitalization or treatment with IV
             antibiotics within four weeks of screening or oral antibiotics within two weeks prior
             to screening visit

          -  Active tuberculosis (TB) requiring treatment within 3 years prior to baseline

          -  Latent TB diagnosed during screening that has not been appropriately treated

          -  Primary or secondary immunodeficiency (history of or currently active)

          -  Moderate to severe heart failure

          -  Evidence of active malignant disease, malignancies diagnosed within the previous 10
             years (including hematologic malignancies and solid tumors, except basal cell
             carcinoma of the skin that has been excised and cured), or breast cancer diagnosed
             within the previous 20 years

          -  Breast feeding mothers

          -  History of alcohol, drug or chemical abuse within the 6 months prior to screening

          -  Participants with lack of peripheral venous access

          -  Participants with a history of allergic reactions to latex

          -  Previous treatment with non-tumor necrosis factor (non-TNF)-inhibitor biologic therapy

          -  Treatment with any investigational agent within 4 weeks of screening visit

          -  Treatment with any cell depleting therapies within 1 year of baseline

          -  Treatment with IV gamma globulin, plasmapheresis or Prosorba column within 6 months of
             baseline visit

          -  Immunization with a live/attenuated vaccine within 4 weeks prior to baseline visit

          -  Any previous treatment with alkylating agents, such as cyclophosphamide or
             chlorambucil, or with total lymphoid irradiation