A Study of Tocilizumab in Comparison to Etanercept in Participants With Rheumatoid Arthritis and Cardiovascular Disease Risk Factors

Phase 4

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: Tocilizumab
Drug: Etanercept

Registration Number: NCT01331837

Lead Sponsor: Hoffmann-La Roche

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3080

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tocilizumab	Tocilizumab	-
Etanercept	Etanercept	-

Primary Outcome Measures

Name	Time	Method
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 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
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).
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 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
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

Secondary Outcome Measures

Name	Time	Method
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.
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: 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
Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Stroke	From baseline up to 4.9 years
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
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
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

Trial Locations

Locations (426): 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
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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
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Uni Of Alabama,Birmingham; Medicine - Rheumatology
🇺🇸Birmingham, Alabama, United States