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

Roche

Status and phase

Completed

Phase 4

Conditions

Rheumatoid Arthritis

Treatments

Drug: Tocilizumab

Drug: Etanercept

Study type

Interventional

Funder types

Industry

Identifiers

NCT01331837

WA25204

2010-020065-24 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment

3,080 patients

Sex

All

Ages

50+ years old

Volunteers

No Healthy Volunteers

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