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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
3,080
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.
Time to First Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event
Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke.
Time frame: From baseline up to 4.9 years
Percentage of Patients Reporting a Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event
Percentage of patients reporting any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke
Time frame: From baseline up to 4.9 years
Time to First CV-EAC Adjudicated Event - Sensitivity Analysis
Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analysis
Time frame: From Baseline up to 4.9 years
Percentage of Patients With a CV-EAC Adjudicated Event - Sensitivity Analysis
Percentage of patients with any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analysis
Time frame: From Baseline up to 4.9 years
Time to First CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis
Prospective comparison of time to first occurrence of any component of the composite of CV death (excluding events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analyses
Time frame: From baseline up to 4.9 years
Percentage of Patients With a CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis
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Uni Of Alabama,Birmingham; Medicine - Rheumatology
Birmingham, Alabama, United States
Rheumatology Associates of North Alabama
Huntsville, Alabama, United States
Clinical and Translational Research Center of Alabama, PC
Tuscaloosa, Alabama, United States
Arizona Arthritis & Rheumatology Associates, P.C.
Glendale, Arizona, United States
Arizona Arthritis & Rheumatology Research, Pllc
Paradise Valley, Arizona, United States
Sun Valley Arthritis Center
Peoria, Arizona, United States
Valley Arthritis Care
Phoenix, Arizona, United States
Advanced Arthritis Care & Research
Scottsdale, Arizona, United States
Camp Lowell Medical Specialists
Tucson, Arizona, United States
The University of Arizona
Tucson, Arizona, United States
...and 418 more locations
Percentage of patients with any component of the composite of CV death (excluding events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analyses
Time frame: From baseline up to 4.9 years
Time to First CV-EAC Adjudicated Event Before Last Direct Contact Date
Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke before last direct contact date (i.e., latest date of visit, IVRS call, or site call).
Time frame: From Baseline up to 4.9 years
Percentage of Participants With a CV-EAC Adjudicated Event Before Last Direct Contact Date
Percentage of participants with any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke before last direct contact date (i.e., latest date of visit, IVRS call, or site call).
Time frame: From Baseline up to 4.9 years
The Time to First Occurrence of an Expanded CV Composite Endpoint
Prospective comparison of the time to first ccurrence of the expanded composite endpoint. The expanded composite endpoint is defined as the CV composite of the primary endpoint with the addition of non-elective coronary revascularization procedures and hospitalization for unstable angina.
Time frame: From baseline up to 4.9 years
Percentages of Participants With an Expanded CV Composite Endpoint
Percentages of participants with the expanded CV composite endpoint. The expanded composite endpoint is defined as the CV composite of the primary endpoint with the addition of non-elective coronary revascularization procedures and hospitalization for unstable angina.
Time frame: From baseline up to 4.9 years
Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction
Prospective comparison of time to first occurrence of Individual component of primary endpoint: non-fatal Myocardial Infarction
Time frame: From baseline up to 4.9 years
Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction
Percentage of patients reporting Individual component of primary endpoint: non-fatal Myocardial Infarction
Time frame: From baseline up to 4.9 years
Time to First Occurrence of Individual Component of Primary Endpoint: Cardiovascular Death
Prospective comparison of time to first occurrence of Individual component of primary endpoint: cardiovascular death
Time frame: From baseline up to 4.9 years
Percentage of Patients With Individual Component of Primary Endpoint: Cardiovascular Death
Percentage of patients reporting Individual component of primary endpoint: cardiovascular death
Time frame: From baseline up to 4.9 years
Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Stroke
Prospective comparison of time to first occurrence of Individual component of primary endpoint: non-fatal stroke
Time frame: From baseline up to 4.9 years
Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Stroke
Time frame: From baseline up to 4.9 years
Time to First Occurrence of Individual Component of Primary Endpoint: All-cause Mortality
Prospective comparison of time to first occurrence of Individual component of primary endpoint: All-cause mortality
Time frame: From baseline up to 4.9 years
Percentage of Patients With Individual Component of Primary Endpoint: All-cause Mortality
Percentage of patients reporting Individual component of primary endpoint: All-cause mortality
Time frame: From baseline up to 4.9 years