The Immunological Basis for Treatment Resistance to Anti-TNF Treatments

Inclusion Criteria: * At least 18 years of age at screening. * Clinically stable moderate to severe plaque psoriasis at screening and baseline. * Subject must be: * A man or * A woman who is surgically sterile or at least 3 years postmenopausal or * A woman of childbearing potential who has had a negative pregnancy test within 7 days before the first dose of study drug. * If the subject is sexually active, (s)he must agree to use a medically acceptable form of contraception during screening and throughout the study. Exclusion Criteria: * Grade 3 or 4 adverse events or infections within 28 days before screening, or between the screening visit and drug initiation. * Active or chronic infection within 4 weeks before screening visit, or between the screening and baseline visits. * Evidence of skin conditions other than psoriasis that would interfere with the evaluations of the effect of study medication on psoriasis. * Use of oral psoralen with ultraviolet A (PUVA), oral retinoids, cyclosporine, alefacept, or any other systemic anti-psoriasis therapy within 28 days study drug initiation. * Use of ulltraviolet B (UVB) therapy, topical steroids at no higher than moderate strength, topical vitamin A or D analog preparations, or anthralin with 14 days of study initiation. * Prior or concurrent use of cyclophosphamide therapy * Concurrent sulfasalazine therapy. * Known hypersensitivity to Enbrel® (etanercept) or any of its components or known to have antibodies to etanercept. * Current enrollment in any other investigational device or investigational drug trial(s), or receipt of any other investigational agent(s) within 28 days before baseline visit. * Use of any biologic drugs within 28 days of study drug initiation. * Concurrent use of Anakinra. * Severe comorbidities (diabetes mellitus requiring insulin; congestive heart failure (CHF) of any severity or myocardial infarction or cerebrovascular accident or transient ischemic attack within 3 months of screening visit; unstable angina pectoris, uncontrolled hypertension (sitting systolic blood pressure (BP) \<80 mm Hg or \> 160 or diastolic BP \> 100 mm Hg), oxygen-dependent severe pulmonary disease, history of cancer within 5 years (other than resected cutaneous basal or squamous cell carcinoma of the skin or in situ cervical cancer) * Known history of tuberculosis (TB), or previous positive purified protein derivative (PPD) test. Any mycobacterial disease or high risk factors for tuberculosis (TB), such as family member with TB, positive purified protein derivative (PPD) or taking anti-tuberculosis medication. * Known HIV-positive status or known history of any other immuno-suppressing disease. * 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. * Latex sensitivity \[Nota Bene: only applicable if they are using prefilled syringe or prefilled SureClick™ autoinjector presentations\] * Exposure to hepatitis B or hepatitis C or to high risk factors for hepatitis B or C, such as intravenous drug use in patient. * Systemic lupus erythematosus, history of multiple sclerosis, transverse myelitis, optic neuritis or seizure disorder. * Use of a live vaccine 90 days prior to screening visit, or concurrent use of a live vaccine. * Any condition or circumstances judged by the patient's physician\[or the investigator or medically qualified study staff\] to render this clinical trial detrimental or otherwise unsuitable for the patient's participation. * History of non-compliance with other therapies. * Pregnant or nursing females. * Diagnosis of multiple sclerosis in first degree family relationship (parent, sibling or child)