MAP Study: Methotrexate and Adalimumab in Psoriasis

Assess the efficacy and safety of ADA compared to ADA/MTX in patients with psoriasis. Many
studies of ADA in rheumatoid and psoriatic arthritis have allowed patients on stable doses of
MTX to continue on MTX while being treated with ADA. There has been no prospective trial of
MTX and ADA concomitantly in psoriasis. Safety of ADA monotherapy vs. combination ADA/MTX
will be compared.

Compare anti-ADA antibody formation and serum ADA levels in patients on ADA compared with
those on combination ADA and MTX. ADA is a fully human monoclonal antibody to TNF-a. More
recent advances in detection of ADA antibodies have shown that many patients develop
antibodies to ADA while on treatment and some of these antibodies are neutralizing. The
presence of anti-ADA antibodies has been correlated with loss of therapeutic response in many
disease states.

Inclusion Criteria:

1. Male or female adult (≥ 18yrs) with a diagnosis of moderate to severe plaque psoriasis

2. Subject must have ≥ 10% body surface area involvement

3. Subject must have psoriasis area and severity index (PASI) ≥12

4. Subject has stable psoriasis of at least six months' duration

5. Male subjects must agree to use a reliable form of birth control during the study and
for 180 days after the last dose of study drug. Male subjects must not donate sperm
during the study or for 180 days after the last dose of study drug. If female, subject
is either not of childbearing potential (postmenopausal for at least 1 year or
surgically sterile) or is of childbearing potential and is using approved method of
birth control throughout study and for 180 days after last dose of study drug.
Approved methods of birth control include the following:

1. Condoms, sponge, foams, jellies, diaphragm, or intrauterine device (IUD)

2. Hormonal contraceptives for 90 days prior to study drug administration

3. A vasectomized partner

6. Subject has negative PPD tuberculosis skin test at screening assessment.

7. Subject must be able and willing to provide written informed consent and comply with
requirements of this study protocol.

Exclusion Criteria

1. Diagnosis or presence of guttate, erythrodermic or pustular psoriasis

2. Any previous exposure to ADA including biosimilar ADA

3. Moderate to high strength topical steroids (class 4 or greater) or Vitamin D analogues
within one week of study entry

4. Oral systemic therapy (methotrexate, cyclosporine, apremilast, acitretin) within 8
weeks of study entry

5. Previous intolerance or adverse reaction to MTX

6. Phototherapy of any type within 4 weeks of study entry (narrowband UVB, psoralen-UVA,
308 nM LASER, commercial tanning units)

7. IL-12/23 inhibitors (ustekinumab) and any IL-23 inhibitor (guselkumab, tildrakizumab,
risankizumab) within 12 weeks of baseline

8. Other biologic agents within 8 weeks of study entry

9. History of chronic liver disease, hepatitis, or alcohol abuse

10. Chronic use of any concomitant medication which has a significant potential for
interaction with MTX (e.g. sulfa antibiotics, chronic non-steroidal anti-inflammatory
(NSAID) use)

11. History of tuberculosis, opportunistic infections, or any active infection at
screening

12. Elevated liver enzymes (AST, ALT, ≥1.5 times normal at screening)

13. Serum creatinine ≥1.5 (at screening)

14. Any other laboratory abnormality that would pose a concern for the investigator

15. Daily alcohol use or consumption of more than four alcoholic drinks (4 ounces) in one
24 hour period

16. Patients who test positive for hepatitis B or C exposure (previous vaccination to
Hepatitis B is allowed)

17. Cancer within the last five years is exclusionary with the exception of treated
cutaneous basal cell carcinoma or squamous cell carcinoma or low-grade cervical
intraepithelial neoplasia.

18. Any patient that is deemed by the investigator to be at a safety risk for the
intervention in this trial.