Mechanism of Action Study for Psoriasis

Inclusion Criteria: * Adults 18-85 years of age with moderate to severe psoriasis, in general good health as determined by the PI based upon the results of medical history, laboratory profile, and physical examination, and who are candidates for systemic or phototherapy * Presence of a psoriatic plaque of \>2cm in an area which can be biopsied repeatedly. * Men must agree to avoid impregnating a woman while on this study. * Women are eligible to participate in the study if they meet one of the following criteria: * Women who are postmenopausal (\>1 year), sterile, or hysterectomized * Women of childbearing potential must undergo monthly pregnancy testing during the study and agree to use two of the following methods of contraception throughout and for 60 days after the last dose of study drug: * Oral contraceptives * Transdermal contraceptives * Injectable or implantable methods * Intrauterine devices * Barrier methods (diaphragm or condom with spermicide) * Abstinence and Tubal Ligation are also considered a form of Birth control Exclusion Criteria: * Patients \<18 or \>85 years old * Absence of a psoriatic plaque \>2cm in diameter * Active guttate, erythrodermic, or pustular psoriasis at the time of the screening visit * Evidence of skin conditions at screening (e.g. eczema) that would interfere with evaluations of the effect of study medication * Inability to understand the consent process * Receipt of any investigational drugs, psoralen+ultraviolet A or oral systemic treatments within 4 weeks of study drug initiation * Biologics within 3 months of study initiation * Topical steroids, topical vitamin A or D analog preparations, Ultraviolet B therapy or anthralin within 2 weeks of study drug initiation. (Exception-stable regimen of class I-II topical steroids on scalp, axillae, and groin) * Methotrexate within 6 weeks of study initiation * History of treatment with adalimumab * History of primary non-response to methotrexate, infliximab or etanercept * History of discontinuation of methotrexate or tumor necrosis factor (TNF) blocker for a safety-related reason that makes it unwise to restart either type of drug * Any internal malignancy within 5 years (excluding fully excised cutaneous basal cell or squamous cell carcinoma) * Pregnancy, not practicing effective birth control, or inability to practice safe sex during the length of the study * Lactation * Subjects who have known hypersensitivity to adalimumab or methotrexate or any of its components or who is known to have antibodies to etanercept * History of alcohol or drug abuse one year before and during the study * Known HIV-positive status or any other immune-suppressing disease * Presence of a grade 3 or 4 infection \<30 days prior to the screening visit, between the screening visit and the first day of treatment on study, or any time during the study that in the opinion of the PI would preclude participation in the study * Any grade 3 or 4 adverse event, or laboratory toxicity, at the time of the screening visit or at any time during the study, which in the opinion of the PI would, preclude participation in the study * Serum creatinine \>3.0 mg/dL (265 micromoles/L) * Serum potassium \<3.5 mmol/L or \> 5.5 mmol/L * Serum alanine aminotransferase or aspartate aminotransferase \>3 times the upper limit of normal for the lab * Platelet count \<100,000/mm3 * White blood cell count \<3,000/mm3 * Hgb, Hct, or red blood cell outside 30% of the upper or lower limits of normal for the Lab * Receipt of live vaccines 1 month prior to or while on study * History of tuberculosis, and/or a positive PPD skin test/chest x-ray at screening without appropriate treatment-treatment of latent tuberculosis (for those with positive PPD tests) must be initiated prior to therapy with adalimumab or methotrexate * Chronic hepatitis B or C infection, history of multiple sclerosis, transverse myelitis, optic neuritis or epilepsy