Mechanism of Action Study for Psoriasis
Condition: Psoriasis
MeSH terms: Psoriasis
Intervention: Methotrexate; Adalimumab (Humira)
Intervention description: 2 cohorts (Randomized 1:1 adalimumab:methotrexate). Subjects will receive treatment on Day 1 (baseline visit) and then weekly or every 2 weeks for 16 weeks.
Methotrexate-treated patients will then receive 16 weeks of adalimumab at the end of study.; 2 cohorts (Randomized 1:1 adalimumab:methotrexate). Subjects will receive treatment on Day 1 (baseline visit) and then weekly or every 2 weeks for 16 weeks.
Intervention MeSH terms: Folic Acid; Adalimumab; Methotrexate
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: tumor necrosis factor (TNF) inhibitor; tumor necrosis factor (TNF) blockade; Methotrexate; treatment; mechanism; psoriasis

Summary:

      The objective of this study is to compare the mechanism of action between adalimumab and
      methotrexate in subjects with psoriasis.
    

Eligibility criteria:

        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