Cytokines and Vascular Inflammation in Psoriasis

Baseline frozen serum samples will be identified from the 107 enrolled Inno-6025 (Abbvie A13-935) (ClinicalTrials.gov Identifier NCT01722214) patients who also underwent a pre-adalimumab FDG-PET scan for the study. Serum cytokine and chemokine levels in these samples will be measured; IL-17 and IL-22 using the Singulex immunoassay platform, and S100A9, IL-6 and TNF alpha using multiplex ELISA. Vascular inflammation will be measured as the target to background ratio (TBR) in the ascending aorta using PET-scan technology. Correlation analyses will be performed between serum levels of cytokines and a chemokine and vascular inflammation.

Inclusion criteria

• Patient has plaque psoriasis.
• Patient has at least a 6 month history of plaque psoriasis.
• Patient has a Body Surface Area (BSA) covered with psoriasis of 5% or more at Day 0.
• Patient is a candidate for systemic therapy.
• Patient is male or female, 18 to 80 years of age at time of consent.
• Patient's weight at screening is a maximum of 180 kg.
• Patient using medication to control angina, hypertension, serum lipids and any medication that can have an effect on inflammation must be on a stable dose for at least 8 weeks before Day 0.
• Patient has an ascending aorta atherosclerotic plaque inflammation target-to-background ratio of 1.6 or more as determined by 18-FDG uptake measured by PET scanning.
• Patient or patient's partner has been in a menopausal state for at least a year, is surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation or vasectomy), is clinically diagnosed infertile, has a same-sex partner, is abstinent, or is willing to use effective contraceptive method for at least 30 days before Day 0 and at least 6 months after the last study drug administration. Effective contraceptive methods are:

• Barrier methods such as condom, sponge or diaphragm combined with spermicide in foam, gel or cream;
• Hormonal contraception (oral, intramuscular, implant or transdermal) which include Depo-Provera, Evra and Nuvaring;
• Intrauterine device (IUD);
• Female patients of childbearing potential must have a negative serum pregnancy test at the Screening visit.
• Patient is judged to be in good general health as determined by the principal investigator based upon the results of medical history, laboratory profile, physical examination, and Chest X-Ray (CXR) performed at Screening.
• Patient will be evaluated for latent TB infection with a purified protein derivative (PPD) or a Quantiferon Gold test and CXR. Patient who demonstrates evidence of latent TB infection (either PPD more than or equal to 5 mm of induration or positive Quantiferon Gold, irrespective of Bacillus Calmette-Guerin (BCG) vaccination status and negative CXR findings for active TB, and/or suspicious CXR findings) will not be allowed to participate in the study.
• Patient must be able and willing to provide written informed consent and comply with the requirements of this study protocol.
• Patient must be able and willing to self-administer subcutaneous (SC) injections or have a qualified person available to administer SC injections.

Exclusion criteria

• Patient has spontaneously improving or rapidly deteriorating plaque psoriasis.
• Patient has other active infections (bacterial, fungal or viral) or skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis or with patient's safety.
• Patient has a history of an allergic reaction or significant sensitivity to constituents of study drug, including latex (a component of the pre-filled syringe).
• Patient has used a non-biological systemic therapy for the treatment of psoriasis less than 30 days before Day 0.
• Patient has used an investigational chemical or biological agent less than 30 days or 5 half-lives prior to the Day 0 visit (whichever is longer).
• Patient has used a biological therapy for the treatment of psoriasis less than 90 days before day 0.
• Patient has used a systemic immunosuppressor (eg. Azathioprine, 6-mercaptopurine) less than 30 days before Day 0.
• Patient is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.
• Patient has used a topical treatment for psoriasis or has used phototherapy within the last 2 weeks prior to Day 0 (at the exception of low potency topical corticosteroids for groin, genitals, face, inframammary area, palms and soles).
• Patient has received Anakinra/Kineret within the last 2 weeks prior to the Day 0 visit or is likely to receive Anakinra/Kineret during the course of the study
• Patient has a poorly controlled medical condition, such as uncontrolled diabetes, documented history of recurrent infections, unstable ischemic heart disease, class III or IV (New York Heart Association Functional Classification; NYHA) congestive heart failure, an ejection fraction of less than 30%, recent stroke (within the past 3 months), chronic leg ulcer or any other condition which, in the opinion of the investigator, would put the patient at risk if participating in the study.
• Patient has had a myocardial infarction or has been hospitalized for a cardiac condition within the past 12 weeks.
• Patient has a history of acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass graft, carotid endarterectomy, stent installation or carotid revascularization within 12 weeks of Day 0.
• Patient has had a percutaneous coronary intervention in the past 12 months.
• Patient plans for a change in medical treatment for angina, serum lipids, hypertension or any other medication that can have a significant effect on inflammation during the course of the study.
• Patient has history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease (e.g. optic neuritis, visual disturbance, gait disorder/ataxia, facial paresis, apraxia).
• Patient has history of cancer or lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix.
• Patient has a history of listeriosis, treated or untreated Tuberculosis (TB), persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous anti-infectives within 30 days prior to the Day 0 visit or oral anti-infectives within 14 days prior to the Day 0 visit.
• Patient has received a live attenuated vaccine 28 days or less before Day 0 or plan to receive a live attenuated vaccine during the study and up to 4 months after the last study drug administration..
• Patient with hepatitis B or hepatitis C viral infection
• Patient with any of the following: hemoglobin ≤ 10 g/L, white blood cell count ≤ 3.0 X 109/L, platelet count ≤130 X 10^9/L, alanine transaminase (ALT) ≥ 2 times the upper limit of normal, aspartate transaminase (AST) ≥ 3 times the upper normal limit, total bilirubin ≥ 2 times the upper normal limit or creatinine ≥ 150 µmol/L.
• Patient currently uses or plans to use anti-retroviral therapy at any time during the study.
• Patient is known to have immune deficiency or is immunocompromised.
• Female patient who is pregnant or breast-feeding or considering becoming pregnant during the study or for 6 months after the last dose of study medication.
• Patient has a history of clinically significant drug or alcohol abuse in the last year.
• Patient who plans to travel in an area where tuberculosis is endemic during the study and up to 4 months after the last study drug administration.
• Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.