Evaluating Efficacy and Safety of Etanercept 50 mg Twice Weekly (BIW) in Rheumatoid Arthritis (RA) Subjects who are Sub-Optimal Responders to Etanercept 50 mg Once Weekly (QW)

- Diagnosis of Rheumatoid Arthritis - RA with a disease duration > 6 months - Current and prior but continuous etanercept (50 mg weekly) treatment for at least 5 months prior to screening - Subjects must be receiving methotrexate (MTX) at a stable dose > 15 mg/week at least 4 weeks prior to screening - Sub-optimal response to etanercept defined by the presence of the following criteria (based on 28 joint count) at screening: 5 or more swollen joints and 5 or more tender joints - Subjects who are currently receiving oral corticosteroids must be on a dose equivalent to prednisone less than or equal to 10 mg/day at screening - Subjects who are currently receiving non-steroidal anti-inflammatory drugs (NSAIDs), must be on a stable dose for at least 2 weeks prior to screening - Subjects who are currently receiving DMARD therapy (including sulfasalazine, hydroxy-chloroquine and leflunomide), must be on a stable dose for at least 4 weeks prior to screening

- Nursing mothers, female subjects planning on becoming pregnant, or male subjects planning a pregnancy with their spouse/partner while in the study - ACR functional class IV - Receipt of any investigational drug or biologic within 4 weeks of study drug initiation - Concurrent or history of psychiatric disease that would interfere with ability to comply with study protocol or give informed consent - History of alcohol or drug abuse within 12 months of screening visit - Severe comorbidities including: History of cancer (other than resected cutaneous basal and squamous cell carcinoma, and in situ cervical cancer) within 5 years of screening visit. Documentation of disease-free state since treatment required; Diagnosis of Class III or IV congestive heart failure (CHF) or myocardial infarction (MI) within 12 months of screening; Unstable or stable angina pectoris; Uncontrolled hypertension (defined as systolic blood pressure measurement of greater than 180 mm Hg or a diastolic blood pressure of greater than 110 mm Hg); Oxygen-dependent pulmonary disease; Known HIV-positive status or other immunodeficiency syndromes; Chronic hepatitis B (HbsAg) or C (HCV); Systemic lupus erythematosus (SLE); CNS demyelinating events suggestive of multiple sclerosis; Presence of active infection or any underlying diseases that could predispose subjects to infection (e.g., history of recurrent infections, non-healing leg ulcers, advanced or poorly controlled diabetes); Active or prior history of tuberculosis (or known exposure). - Concurrent treatment with cyclophosphamide