Comparative Effectiveness of Psoriasis Treatments on Systemic Inflammation

Study Overview
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Brief Summary
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This is a prospective longitudinal observational pilot study of psoriasis patients on continuous standard-of-care systemic therapeutics to determine the level of change in established (plasma/serum) and investigative (cellular) biomarkers that are associated with increased risk of CVD events. The final endpoint of the proposed study will be a ranking of the examined biomarkers based upon an integrated assessment of biomarker behavior over time. Secondary outcomes will assess changes in coronary artery calcification scoring, PET-MRI, skin biopsies, and clinical improvement.

Official Title
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Comparative Effectiveness of Psoriasis Treatments on Systemic Inflammation

Conditions
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Psoriasis, Inflammation

Intervention / Treatment
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* Drug: Methotrexate
* Drug: Ustekinumab
* Drug: Etanercept
* Drug: Adalimumab
* Drug: Acitretin
* Other: UVB Excimer Laser
* Other: Narrowband UVB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects ages 18-65 years old Diagnosis of moderate-to-severe plaque psoriasis Plaque affects ≥ 10% of subject's body surface area (BSA) Subjects prescribed one of the following standard-of-care treatments for their psoriasis: Ustekinumab, Methotrexate, Etanercept, Adalimumab, Narrow Band UVB (311nm), Excimer Laser Treatment (308nm), or Acitretin Subjects willing to complete a Washout Period prior to Visit 1 (only for subjects currently on a psoriasis treatment): Discontinue systemic therapies for at least 4 weeks Discontinue topical therapies for at least 2 weeks Discontinue phototherapies for at least 2 weeks Exclusion Criteria: Subjects who are currently on a psoriasis treatment and unwilling to go through the washout-period Subjects with a critical illness or who are immunocompromised Weight is 400lbs or greater Subjects who are currently pregnant or breastfeeding Subjects who have metal implants Subjects who have a pacemaker, stent, or artificial heart valve History of clinically significant hematological, renal or liver disease Patients with known co-morbidities that raise biomarkers such as: History of myocardial infarction (MI) History of cerebrovascular accident (CVA) Significant atherosclerosis (defined as the presence of any carotid plaque; or carotid intimal media thickness (cIMT) >75th percentile for age; or the presence of coronary artery calcium score>100) Poorly controlled diabetes (elevated HbA1c > 8.5)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Methotrexate<br>Methotrexate will be dosed weekly. Methotrexate is given as a single, weekly dose and is will be started at 15mg after a first week test dose of 2.5 mg to minimize side effects and achieve efficacy. Weekly dosages will be 15mg. | Drug: Methotrexate<br>* Subjects will receive Methotrexate as detailed in the Group description.<br>|
| Ustekinumab<br>Ustekinumab is given as a subcutaneous injection of 45mg if the patient is <100Kg or 90mg if the patient is >100Kg at weeks 0, 4, 16, and every 12 weeks thereafter. | Drug: Ustekinumab<br>* Subjects will receive Ustekinumab as detailed in the Group description.<br>|
| Etanercept<br>Etanercept will be given in the first 3 months of treatment as 50 mg twice a week (3 or 4 days apart). After 3 months, a reduced dose of 50 mg will be given once per week. | Drug: Etanercept<br>* Subjects will receive Etanercept as detailed in the Group description.<br>|
| Adalimumab<br>Adalimumab will be given in a dose of 40 mg subcutaneously every other week. | Drug: Adalimumab<br>* Subjects will receive Adalimumab as detailed in the Group description.<br>|
| Acitretin<br>Acetretin will be prescribed as daily with 25mg if the patient is <80Kg or 35mg if the patient is >80Kg. | Drug: Acitretin<br>* Subjects will receive Acitretin as detailed in the Group description.<br>|
| UVB Excimer Laser<br>Dose determination will be determined by a physician per standard-of-care by performing a Sunburn Test/Minimal Erythemal Dose Test, or by visually evaluating the patient's skin type and thickness of psoriasis plaque. Initial laser dose will be 1-4X the MED depending on the thickness of the plaque. Escalation will be 25-50% increase in dose per treatment if there is no residual erythema, 25% increase per treatment if there is mild residual erythema, and 0% increase per treatment if there is moderate residual erythema. Investigators also have the option to skip a treatment, if there is above moderate erythema, or significant patient discomfort. Patients will receive treatment twice a week. | Other: UVB Excimer Laser<br>* Subjects will receive UVB Excimer Laser therapy as detailed in the Group description.<br>|
| Narrowband UVB<br>Narrowband UVB (311nm) will be used to treat patients 3X per week with 311nm of UVB light. Uninvolved areas of skin will be covered where possible to minimize excess sun exposure. Patients will be tested for their minimal erythemal dose (MED), after which, based upon Fitzpatrick Scale skin type, a patient will typically beginning with 1-2 minutes based on skin type and gradually increased by 10-15% per treatment dose as tolerated. | Other: Narrowband UVB<br>* Subjects will receive Narrowband UVB as detailed in the Group description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker assessment | The biomarkers examined throughout the study will be assessed. And, an integrated assessment of biomarker behavior over time will be performed. Biomarkers examined will include High sensitivity C-reactive protein (hsCRP), Myeloperoxidase (MPO), resistin, adiponectin and leptin. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in coronary artery calcification scoring | Coronary Artery Calcification Scoring (CACS) will be performed at the first and final visits for the study. | 52 weeks | 
| Changes in PET-MRI | Patients who enroll in this study will receive two PET/MRI scans. The first one will be done prior to beginning their psoriasis therapy during Visit 1 and the second PET/MRI will be done during the Final Visit. | 52 weeks | 
| Clinical improvement | Psoriasis Area Severity Index (PASI) and Static Physician Global Assessment (sPGA) will be performed throughout the study to monitor clinical improvement. | 52 weeks | 
| Changes in skin biopsies | In some patients, two 4-6mm punch biopsies will be obtained after the washout period has been observed, one from a psoriasis lesion and one from an adjacent, uninvolved area. Two 4-6mm punch biopsies will also be obtained during the final visit, one from a psoriasis lesion and one from an adjacent, uninvolved area. | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriasis, comparative effects, inflammation