Addition of Modulators of Homocysteine to Adalimumab Therapy in the Treatment of Moderate to Severe Plaque Psoriasis

This is a pilot study designed to evaluate whether addition of oral vitamin B12, vitamin
B6, and folic acid to the use of adalimumab for psoriasis leads to further improvement of a
patient's psoriasis and quality of life.

Adalimumab is indicated by the Food and Drug Administration (FDA) for the treatment of
adults with moderate to severe long standing (chronic) plaque psoriasis. Adalimumab is a
medicine called a TNF-alpha (tumor necrosis factor alpha) blocker. The extra TNF-alpha in
the body can attack normal healthy body tissues and cause inflammation. The purposes of this
study are to investigate the effects of the addition of 12 weeks of modulators of
homocysteine (oral vitamin B12, oral vitamin B6 or pyridoxine, and oral folic acid) plus
adalimumab after 16 weeks adalimumab therapy on the clinical appearance of psoriasis and on
laboratory values correlated with the use and disuse of said modulators. Given that near
maximum clinical improvement on adalimumab is expected after 16 weeks of adalimumab, if
further clearcut improvement was seen in most subjects at the 28 week visit, it would be
attributed to the addition of the vitamins.

Inclusion Criteria:

- adults 18 or older

- moderate to severe plaque psoriasis (>10% BSA)

- Negative pregnancy test within 7 days before first dose of adalimumab in all women
(except surgically sterile or 5 years postmenopausal)

- subject must sign/date appropriate written informed consent&HIPAA authorization

- Sexually active subjects of childbearing potential must agree to use medically
acceptable contraception during screening and throughout the study

- no evidence of active or latent tuberculosis based on a negative PPD skin test
performed at screening, or within one year of starting this study. Patients with
documentation of adequately treated TB may be enrolled

- Patients PPD positive and CXR negative can be enrolled if they finish appropriate INH
prophylaxis prior to enrollment

- be willing and able to self-administer subcutaneous injections or to have a qualified
person available to administer these injections

- agrees to comply with protocol requirements, attend all regularly study visits and is
considered to be a good study subject

- meets concomitant medication washout requirements

- willing to use only allowed psoriasis medications and treatments and agree not to
start any topical, systemic, or phototherapy for psoriasis during the study period

- adalimumab naïve

Exclusion Criteria:

- erythrodermic, pustular, or guttate psoriasis

- skin conditions other than psoriasis that would interfere with study-related
psoriasis evaluations

- known sensitivity to any component of the study medications

- Evidence of active infections such as fevers, chills, sweats, or history of untreated
Lyme disease and active severe infections within 4 weeks before screening visit, or
between the screening and Week 0 visits

- history of listeriosis, untreated TB, persistent or active infections requiring
hospitalization or treatment with IV antibiotics, IV antiretrovirals, or IV
antifungals within 30 days of baseline, OR oral antibiotics, antivirals, or
antifungals for purpose of treating infection, within 14 days of baseline

- positive PPD and positive chest x-ray for latent or active tuberculosis

- positive PPD and negative chest x-ray that have not completed appropriate INH
prophylaxis

- On immune compromising drug or history of immune compromising disorder or
immunodeficiency

- poorly controlled medical condition including, not limited to, unstable
cardiovascular disease, poorly controlled diabetes, recent stroke, history of
recurrent infections, or any condition for which, in the opinion of the
investigators, participation in the study would place the subject at risk

- hx. congestive heart failure

- hx. demyelinating CNS disease

- History of malignancy (other than previously treated localized carcinoma in situ of
the cervix or previously treated nonmelanoma skin cancer)

- history of or ongoing drug or alcohol abuse

- past or present psychiatric morbidity which may compromise the study

- Pregnant women, nursing mothers, or planning to become pregnant during study or
within 150 days after last dose of study medication. Males planning pregnancy with
spouse/partner while in study are to be excluded

- plans to receive any live vaccines during study

- history of liver disease

- Current enrollment in another clinical study/treatment with other experimental drug
or approved therapy for experimental use within 30 days prior to Week 0

- previous enrollment in this study

- cannot commit to all assessments required by the protocol

- disorder that compromises the subject to give written informed consent and/or comply
with study procedures

- considered by the investigators to be unsuitable candidate

- cannot comply with the protocol washout requirements

- on folic acid in doses over than the minimal daily requirements

- on vitamins higher than minimal daily requirements (multivitamins are allowed)

- colon polyps or cancer

- prior adalimumab therapy

- on screening plasma Vascular Endothelial Growth Factor level is 140 pg/ml or more