Rheumatoid Arthritis
Conditions
Brief 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).
Interventions
DRUGEtanercept
Participants will receive 50 mg etanercept subcutaneously weekly until switch to another RA therapy or up to 4.9 years.
DRUGTocilizumab
Participants will receive 8 mg/kg tocilizumab IV every 4 weeks until switch to another RA therapy or up to 4.9 years.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event | From baseline up to 4.9 years | 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. |
| Percentage of Patients Reporting a Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event | From baseline up to 4.9 years | 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 to First CV-EAC Adjudicated Event - Sensitivity Analysis | From Baseline up to 4.9 years | 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 |
| Percentage of Patients With a CV-EAC Adjudicated Event - Sensitivity Analysis | From Baseline up to 4.9 years | 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 to First CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis | From baseline up to 4.9 years | 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 |
| Percentage of Patients With a CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis | From baseline up to 4.9 years | 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 to First CV-EAC Adjudicated Event Before Last Direct Contact Date | From Baseline up to 4.9 years | 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). |
| Percentage of Participants With a CV-EAC Adjudicated Event Before Last Direct Contact Date | From Baseline up to 4.9 years | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Occurrence of Individual Component of Primary Endpoint: All-cause Mortality | From baseline up to 4.9 years | Prospective comparison of time to first occurrence of Individual component of primary endpoint: All-cause mortality |
| Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction | From baseline up to 4.9 years | Prospective comparison of time to first occurrence of Individual component of primary endpoint: non-fatal Myocardial Infarction |
| Percentage of Patients With Individual Component of Primary Endpoint: All-cause Mortality | From baseline up to 4.9 years | Percentage of patients reporting Individual component of primary endpoint: All-cause mortality |
| The Time to First Occurrence of an Expanded CV Composite Endpoint | From baseline up to 4.9 years | 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. |
| Percentages of Participants With an Expanded CV Composite Endpoint | From baseline up to 4.9 years | 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. |
| Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction | From baseline up to 4.9 years | Percentage of patients reporting Individual component of primary endpoint: non-fatal Myocardial Infarction |
| Time to First Occurrence of Individual Component of Primary Endpoint: Cardiovascular Death | From baseline up to 4.9 years | Prospective comparison of time to first occurrence of Individual component of primary endpoint: cardiovascular death |
| Percentage of Patients With Individual Component of Primary Endpoint: Cardiovascular Death | From baseline up to 4.9 years | Percentage of patients reporting Individual component of primary endpoint: cardiovascular death |
| Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Stroke | From baseline up to 4.9 years | Prospective comparison of time to first occurrence of Individual component of primary endpoint: non-fatal stroke |
| Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Stroke | From baseline up to 4.9 years | — |
Countries
Argentina, Austria, Belgium, Bosnia and Herzegovina, Canada, Chile, Croatia, Czechia, Ecuador, France, Germany, Greece, Hungary, India, Israel, Italy, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Philippines, Poland, Romania, Russia, Serbia, South Africa, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
A total of 3080 patients were enrolled from 353 sites, across 31 countries
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Participants received 8 mg/kg tocilizumab IV every 4 weeks until switch to another RA therapy or up to 4.9 years. | 1,538 |
| Etanercept Participants received 50 mg etanercept subcutaneously weekly until switch to another RA therapy or up to 4.9 years. | 1,542 |
| Total | 3,080 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 30 | 34 |
| Overall Study | Info not recorded | 10 | 16 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Withdrawal by Subject | 13 | 16 |
Baseline characteristics
| Characteristic | Tocilizumab | Etanercept | Total |
|---|---|---|---|
| Age, Continuous | 60.7 Years STANDARD_DEVIATION 7.4 | 60.7 Years STANDARD_DEVIATION 7.6 | 60.7 Years STANDARD_DEVIATION 7.5 |
| Sex: Female, Male Female | 1193 Participants | 1202 Participants | 2395 Participants |
| Sex: Female, Male Male | 345 Participants | 340 Participants | 685 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 910 / 1,542 | 1,090 / 1,538 |
| serious Total, serious adverse events | 422 / 1,542 | 479 / 1,538 |
Outcome results
Primary
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
Population: Analysis was conducted on the ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants With a CV-EAC Adjudicated Event Before Last Direct Contact Date | 3.2 Percentage of participants with event |
| Etanercept | Percentage of Participants With a CV-EAC Adjudicated Event Before Last Direct Contact Date | 3.0 Percentage of participants with event |
Primary
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
Population: Analysis was conducted on the Intention to treat (ITT) population, i.e. all patients randomized who have taken at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Patients Reporting a Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event | 5.4 Percentage of patients with event |
| Etanercept | Percentage of Patients Reporting a Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event | 5.1 Percentage of patients with event |
Primary
Percentage of Patients With a CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis
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
Population: Analysis was conducted on the ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Patients With a CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis | 4.8 Percentage of patients with event |
| Etanercept | Percentage of Patients With a CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis | 4.7 Percentage of patients with event |
Primary
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
Population: Analyses was conducted on the On-treatment (OT) population, i.e. patients who switched from randomized treatment were censored at the time of treatment switching.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Patients With a CV-EAC Adjudicated Event - Sensitivity Analysis | 3.7 Percentage of patients with event |
| Etanercept | Percentage of Patients With a CV-EAC Adjudicated Event - Sensitivity Analysis | 3.4 Percentage of patients with event |
Primary
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
Population: Analysis was conducted on the Intention to treat (ITT) population, i.e. all patients randomized who have taken at least one dose of study medication
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Time to First Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event | NA Months |
| Etanercept | Time to First Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event | NA Months |
Comparison: The analysis assessed in the ITT population the hazard ratio of the primary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients.~A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata:~* Previous exposure to anti-TNF (Yes/No)~* History of CV events (Yes/No)95% CI: [0.77, 1.43]
Primary
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
Population: Analysis was conducted on the ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Time to First CV-EAC Adjudicated Event Before Last Direct Contact Date | NA Months |
| Etanercept | Time to First CV-EAC Adjudicated Event Before Last Direct Contact Date | NA Months |
Comparison: The analysis assessed in the ITT population the hazard ratio of the primary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients.~A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata:~* Previous exposure to anti-TNF (Yes/No)~* History of CV events (Yes/No)95% CI: [0.7, 1.56]
Primary
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
Population: Analysis was conducted on the ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Time to First CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis | NA Months |
| Etanercept | Time to First CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis | NA Months |
Comparison: The analysis assessed in the ITT population the hazard ratio of the primary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients.~A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata:~* Previous exposure to anti-TNF (Yes/No)~* History of CV events (Yes/No)95% CI: [0.73, 1.4]
Primary
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
Population: Analyses was conducted on the On-treatment (OT) population, i.e. patients who switched from randomized treatment were censored at the time of treatment switching.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Time to First CV-EAC Adjudicated Event - Sensitivity Analysis | NA Months |
| Etanercept | Time to First CV-EAC Adjudicated Event - Sensitivity Analysis | NA Months |
Comparison: The analysis assessed in the OT population the hazard ratio of the primary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients.~A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata:~* Previous exposure to anti-TNF (Yes/No)~* History of CV events (Yes/No)95% CI: [0.76, 1.62]
Secondary
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
Population: Analysis was conducted on the ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Patients With Individual Component of Primary Endpoint: All-cause Mortality | 4.2 Percentage of patients |
| Etanercept | Percentage of Patients With Individual Component of Primary Endpoint: All-cause Mortality | 4.2 Percentage of patients |
Secondary
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
Population: Analysis was conducted on the ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Patients With Individual Component of Primary Endpoint: Cardiovascular Death | 2.3 Percentage of patients |
| Etanercept | Percentage of Patients With Individual Component of Primary Endpoint: Cardiovascular Death | 2.3 Percentage of patients |
Secondary
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
Population: Anlysis was conducted on the ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction | 1.8 Percentage of patients |
| Etanercept | Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction | 2.0 Percentage of patients |
Secondary
Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Stroke
Time frame: From baseline up to 4.9 years
Population: Analysis was conducted on the ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Stroke | 1.6 Percentage of patients |
| Etanercept | Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Stroke | 1.0 Percentage of patients |
Secondary
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
Population: Analysis was conducted on the ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentages of Participants With an Expanded CV Composite Endpoint | 5.5 Percentages of participants |
| Etanercept | Percentages of Participants With an Expanded CV Composite Endpoint | 5.4 Percentages of participants |
Secondary
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
Population: Analysis was conducted on the ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | The Time to First Occurrence of an Expanded CV Composite Endpoint | NA Months |
| Etanercept | The Time to First Occurrence of an Expanded CV Composite Endpoint | NA Months |
Comparison: The analysis assessed in the ITT population the hazard ratio of the secondary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients.~A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata:~* Previous exposure to anti-TNF (Yes/No)~* History of CV events (Yes/No)95% CI: [0.73, 1.34]
Secondary
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
Population: Analysis was conducted on the ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Time to First Occurrence of Individual Component of Primary Endpoint: All-cause Mortality | NA Months |
| Etanercept | Time to First Occurrence of Individual Component of Primary Endpoint: All-cause Mortality | NA Months |
Comparison: The analysis assessed in the ITT population the hazard ratio of the secondary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients.~A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata:~* Previous exposure to anti-TNF (Yes/No)~* History of CV events (Yes/No)95% CI: [0.7, 1.41]
Secondary
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
Population: Analysis was conducted on the ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Time to First Occurrence of Individual Component of Primary Endpoint: Cardiovascular Death | NA Months |
| Etanercept | Time to First Occurrence of Individual Component of Primary Endpoint: Cardiovascular Death | NA Months |
Comparison: The analysis assessed in the ITT population the hazard ratio of the secondary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients.~A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata:~* Previous exposure to anti-TNF (Yes/No)~* History of CV events (Yes/No)95% CI: [0.64, 1.63]
Secondary
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
Population: Anlysis was conducted on the ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction | NA Months |
| Etanercept | Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction | NA Months |
Comparison: The analysis assessed in the ITT population the hazard ratio of the secondary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients.~A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata:~* Previous exposure to anti-TNF (Yes/No)~* History of CV events (Yes/No)95% CI: [0.54, 1.49]
Secondary
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
Population: Analysis was conducted on the ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tocilizumab | Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Stroke | NA Months |
| Etanercept | Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Stroke | NA Months |
Comparison: The analysis assessed in the ITT population the hazard ratio of the secondary endpoint in TCZ compared to ETA patients. This was done through a comparison of the hazard functions between TCZ and ETA patients.~A stratified Cox proportional hazards regression model was used in evaluating the relative CV event rate of TCZ over ETA, with the following randomization factors used as strata:~* Previous exposure to anti-TNF (Yes/No)~* History of CV events (Yes/No)95% CI: [0.8, 2.92]