Cardiovascular Disease, Psoriasis
Conditions
Keywords
Psoriasis, Cardiovascular Disease, FDG/PET-CT, NB-UVB Phototherapy, Vascular Inflammation, Lipid Biomarkers
Brief summary
The purpose of this study is to assess the effect of adalimumab (Humira), when compared to NB-UVB (narrow-band ultraviolet B) phototherapy or placebo (an inactive substance that may resemble an active substance but has no medical value) injection. The study will compare the effects of each on systemic inflammation and cardiovascular disease risk factors in subjects diagnosed with moderate to severe psoriasis. This study will look for systemic vascular inflammation in subjects with a test called FDG-PET/CT (Fluorodeoxyglucose-positron emission tomography/computed tomography). The study will also look for cardio metabolic (heart disease and metabolic factors such as diabetes) identifiers in the blood. A blood sample will be taken that will look for these markers identifying high cholesterol, cholesterol efflux function (the ability of cholesterol to move in the body), metabolic factors, and inflammation. This study will also assess the effect of adalimumab (Humira), when compared to NB-UVB phototherapy or placebo injection on psoriasis activity and severity. The study will also compare the safety of adalimumab (Humira) to NB-UVB phototherapy or placebo injection. This study will also evaluate subjects' reported outcomes through a questionnaire that will assess quality-of-life in subjects living with psoriasis.
Interventions
Humira will be given at an initial dose of 80mg followed by 40 mg the second week, subsequent doses will be given at 40mg and follow FDA dosing schedule.
DRUGPlacebo Injection
Placebo injection will be given according to the same dose and schedule as the active comparator.
OTHERNB-UVB phototherapy
Phototherapy will be given 3 times per week according to the Fitzpatrick scale for skin types.
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and females 18 years of age and older. 2. Clinical diagnosis of psoriasis for at least 6 months as determined by subject interview of his/her medical history and confirmation of diagnosis through physical examination by Investigator. 3. Stable plaque psoriasis for at least 2 months before Screening and at Baseline (Week 0) as determined by subject interview of his/her medical history. 4. Moderate to severe psoriasis defined by ≥ 10 percent Body Surface Area (BSA) involvement at the Baseline (Week 0) visit. 5. PASI (psoriasis assessment and severity index) score of ≥ 12 at the Baseline (Week 0) visit. 6. Subject is a candidate for systemic therapy or phototherapy and has active psoriasis despite prior treatment with topical agents. 7. Women are eligible to participate in the study if they meet one of the following criteria: 1. Women of childbearing potential who are willing to undergo regular pregnancy testing and agree to use one method of contraception throughout the study are eligible to participate 2. Women who are postmenopausal (for at least one year), sterile, or hysterectomized are eligible to participate 3. Women who have undergone tubal ligation are eligible to participate 4. Women who agree to be sexually abstinent, defined as total abstinence from sexual intercourse, as a form of contraception are eligible to participate in the study. 8. Subject 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 12-lead electrocardiogram (ECG) performed at screening. 9. Able and willing to give written informed consent and to comply with requirements of this study protocol.
Exclusion criteria
1. Previous adverse event following exposure to a TNF-alpha antagonist and/or UV phototherapy that led to discontinuation of either of these therapies and contraindicates future treatment. 2. Previous lack of response to a TNF-alpha antagonist and/or UV phototherapy that led to discontinuation of either of these therapies. 3. Diagnosis of erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis. 4. Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis. 5. Cannot avoid UVB phototherapy for at least 14 days prior to the Baseline (Week 0) visit. 6. Cannot avoid psoralen-UVA phototherapy for at least 30 days prior to the Baseline (Week 0) visit and during the study. 7. Cannot discontinue systemic therapies for the treatment of psoriasis, or systemic therapies known to improve psoriasis, during the study: * Systemic (investigational or marketed) therapies must be discontinued at least 30 days prior to the Baseline (Week 0) visit except for biologics. * All biologics, except ustekinumab, must be discontinued for at least 90 days prior to Baseline (Week 0). * The IL-12/IL-23 antagonist ustekinumab (half-life of 45.6 ± 80.2 days) must be discontinued for at least 180 days prior to Baseline (Week 0). * Investigational agents must be discontinued at least 30 days or 5 half-lives (whichever is longer) prior to the Baseline (Week 0) visit. 8. Subject is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed. 9. Poorly controlled medical condition, such as unstable ischemic heart disease, congestive heart failure, recent cerebrovascular accidents, psychiatric disease requiring frequent hospitalization, and any other condition, which, in the opinion of the Investigator, would put the subject at risk by participation in the study. 10. History of diabetes mellitus, type 1 or type 2 - note that patients with type 2 diabetes may be enrolled if the duration of diabetes is \<10 years and HbA1c is \<7.0%) 11. Uncontrolled hypertension, with measured systolic blood pressure \>180 mmHg or diastolic blood pressure \>90 mmHg 12. History of demyelinating diseases or lupus. 13. Subject has infection or risk factors for severe infections, for example: * Positive serology or known history of HIV, hepatitis B or C, or other severe, recurrent, or persistent infections; * Excessive immunosuppression or other factors associated with it, including human immunodeficiency virus infection; * Active tuberculosis (TB) disease; * Evidence of latent TB infection demonstrated by Purified Protein Derivative (PPD) ≥ 5 mm of induration or positive Quantiferon-GOLD results; except if prophylactic treatment for TB, as recommended by local guidelines, is initiated prior to administration of study drug or if there is documentation that the subject has received prophylactic treatment for TB previously. * Any other significant infection requiring hospitalization or intravenous (IV) antibiotics in the month prior to Baseline; * Infection requiring treatment with oral or parenteral antibiotics within 14 days prior to Baseline; * Subject has received vaccination with Bacille Calmette-Guerin (BCG) within 365 days prior to Screening; * Subject has received vaccination with a live viral agent 30 days prior to Screening or will require a live vaccination during study participation including up to 30 days after the last dose of study drug. 14. Subject has history of hematological or solid malignancy other than successfully treated basal cell carcinoma, non-metastatic cutaneous squamous cell carcinoma or cervical carcinoma in situ. 15. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study. 16. Screening clinical laboratory analyses showing any of the following abnormal results: * Hemoglobin (Hgb) \< 10 g/dL in females or \<12 g/dL in males; * White blood cell (WBC) count \<2.5 x 109/L o Subject can be included if WBC count is \<2.5 x x 109/L and absolute neutrophil count (ANC) is \>1000 cells / mm3. * WBC count \> 15 x 109/L; * Platelet count \< 100 x 109/L; * Serum aspartate transaminase (AST) or alanine transaminase (ALT) \>2.5 upper limits of normal (ULN); * Serum total bilirubin ≥2 mg/dL (≥26 µmol/L); or * Serum creatinine \>1.6 mg/dL (\>141 µmol/L). 17. Recent history of substance abuse or psychiatric illness that could preclude compliance with the protocol. 18. History of any substance abuse within 365 days of screening visit 19. Alcohol use \>14 drinks per week at the screening visit or within 30 days of the screening period 20. If subject is on cholesterol-lowering medication (e.g. statin), dose and form of medication must be stable for 90 days prior to week 0 and remain stable throughout the duration of the study. 21. History of photosensitivity of medical condition that may be exacerbated by UV exposures such as lupus or dermatomyositis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cardiometabolic Biomarkers: GlycA | Baseline - Week 12 | To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on GlycA |
| Change in Cardiometabolic Biomarkers: Log Insulin | Baseline - Week 12 | To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log insulin. |
| Change in Cardiometabolic Biomarkers: Log Adiponectin | Baseline - Week 12 | To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log adiponectin. |
| Change in Cardiometabolic Biomarkers: Log Leptin | Baseline - Week 12 | To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log leptin. |
| Change in Cardiometabolic Biomarkers: Log C-reactive Protein | Baseline - Week 12 | To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log C-reactive protein (CRP). |
| Change in Cardiometabolic Biomarkers: Log Tumor Necrosis Factor-alpha | Baseline - Week 12 | To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log Tumor necrosis factor-alpha. |
| Change in Cardiometabolic Biomarkers: Log Interleukin 6 | Baseline - Week 12 | To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log interleukin 6. |
| Change in Vascular Inflammation | Baseline - Week 12 | Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between baseline and week 12. The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUV mean yielding a target to background ratio (TBR). |
| Change in Cardiometabolic Biomarkers: Total Cholesterol | Baseline - Week 12 | To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on total cholesterol. |
| Change in Cardiometabolic Biomarkers: Cholesterol Efflux | Baseline - Week 12 | To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on cholesterol efflux capacity. The ability to promote cholesterol efflux from macrophages is a classic function of HDL that is thought to be an important mechanism by which HDL protects against atherosclerosis. HDL cholesterol efflux capacity assays are performed based on published methods using J774 cells derived from a murine macrophage cell line (Mehta NN Atherosclerosis 2012). Efflux is calculated as a unitless measure by using the following formula: \[(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)\]. The pooled plasma was obtained from five healthy volunteers. |
| Change in Cardiometabolic Biomarkers: Low Density Lipoprotein Particle Total | Baseline - Week 12 | To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on low density lipoprotein particle total. |
| Change in Cardiometabolic Biomarkers: High Density Lipoprotein Particle Total | Baseline - Week 12 | To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on high density lipoprotein particle total. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Patient-reported Outcomes-EuroQol EQ-5D | Baseline -Week 12 | EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ VAS. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression on a scale ranging from 1 (no health state problem) to 3 (extreme health state problems). The EQ VAS records the patient's self-rated health on a vertical visual analogue scale ranging from 0, worst health state, to 100, best health state. A scoring function is used to assign a value (i.e., EQ-5D™ index score) to self-reported health states from a set of population-based preference weights. For the U.S. general population, the possible EQ-5D index scores range from -0.11 to 1.0 where 0.0 = death and 1.0 = perfect health. |
| Change in Patient-reported Outcomes-Dermatology Life Quality Index (DLQI) | Baseline - Week 12 | Patient reported quality of life outcomes will be assessed using DLQI. The DLQI is calculated by summing the score of 10 questions regarding impact of skin condition on daily life resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. |
| Change in Patient-reported Outcomes-MEDFICTS Dietary Assessment) | Baseline to Week 12 | Patient reported dietary outcomes will be assessed using MEDFICTS (Meats, Eggs, Dairy, Fried foods, fat In baked goods, Convenience foods, fats added at the Table, and Snacks), a brief dietary assessment instrument for properly assessing cardiovascular diet. The questionnaire yields a continuous score (ranging from 0 to 216), with a score of \<40 indicating adherence to the Therapeutic Lifestyle Changes (TLC) diet (intake of \<7% of energy from saturated fat, \<30% of energy from total fat, and \<200 mg dietary cholesterol/day). |
| Change in Patient-reported Outcomes-International Physical Activity Questionnaire (IPAQ) | Baseline week 4, 8 and 12 | Patient reported physical activity will be assessed using IPAQ. IPAQ is an instrument designed primarily for population surveillance of physical activity among adults with activity measured in metabolic equivalent (MET)-minutes per week. |
| Number of Patients With Adverse Events. | Baseline - Week 12 | Safety will be assessed by comparing how many patients have adverse events depending on whether they are on adalimumab, as compared to NB-UVB phototherapy or placebo. |
| Change in Psoriasis Activity (PASI-75 and PGA) | Baseline - Week 12 | Psoriasis activity will be assessed using standard psoriasis measurements, PASI75 and PGA Clear/Almost Clear |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adalimumab (Humira) Injection of the active drug Humira.
Adalimumab (Humira): Humira will be given at an initial dose of 80mg followed by 40 mg the second week, subsequent doses will be given at 40mg and follow FDA dosing schedule. | 33 |
| Placebo Injection Injection of placebo in place of active Humira injection.
Placebo Injection: Placebo injection will be given according to the same dose and schedule as the active comparator. | 31 |
| NB-UVB Phototherapy NB-UVB Phototherapy 3 times per week, no other intervention.
NB-UVB phototherapy: Phototherapy will be given 3 times per week according to the Fitzpatrick scale for skin types. | 33 |
| Total | 97 |
Baseline characteristics
| Characteristic | Total | Adalimumab (Humira) | Placebo Injection | NB-UVB Phototherapy |
|---|---|---|---|---|
| 10year Framingham Risk % | 7.53 percentage STANDARD_DEVIATION 8.09 | 8.43 percentage STANDARD_DEVIATION 7.75 | 7.91 percentage STANDARD_DEVIATION 8.83 | 6.12 percentage STANDARD_DEVIATION 7.68 |
| Age, Continuous | 43.46 years STANDARD_DEVIATION 14.03 | 44.15 years STANDARD_DEVIATION 13.97 | 44.32 years STANDARD_DEVIATION 14.5 | 41.97 years STANDARD_DEVIATION 13.97 |
| Body Mass Index | 31.83 kg/m^2 STANDARD_DEVIATION 7.91 | 30.93 kg/m^2 STANDARD_DEVIATION 7.42 | 31.95 kg/m^2 STANDARD_DEVIATION 7.74 | 32.61 kg/m^2 STANDARD_DEVIATION 8.66 |
| Body Surface Area | 23.98 percentage STANDARD_DEVIATION 14.19 | 23.39 percentage STANDARD_DEVIATION 14.48 | 25.70 percentage STANDARD_DEVIATION 15.02 | 22.96 percentage STANDARD_DEVIATION 13.37 |
| Diabetes | 4 Participants | 3 Participants | 1 Participants | 0 Participants |
| DLQI (Dermatology Quality of Life Index) | 14.68 units on a scale STANDARD_DEVIATION 6.58 | 15.88 units on a scale STANDARD_DEVIATION 5.53 | 13.48 units on a scale STANDARD_DEVIATION 7.58 | 14.61 units on a scale STANDARD_DEVIATION 6.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 5 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 81 Participants | 27 Participants | 28 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| History of Cardiovascular Disease | 7 Participants | 2 Participants | 3 Participants | 2 Participants |
| History of Phototherapy | 29 Participants | 5 Participants | 11 Participants | 13 Participants |
| H/O Biologics | 29 Participants | 10 Participants | 11 Participants | 8 Participants |
| H/O Oral Systemics | 31 Participants | 10 Participants | 10 Participants | 11 Participants |
| Hyperlipidemia | 14 Participants | 5 Participants | 5 Participants | 4 Participants |
| Hypertension | 18 Participants | 6 Participants | 7 Participants | 5 Participants |
| PASI (Psoriasis Area and Severity Index) | 18.85 units on a scale STANDARD_DEVIATION 7.08 | 18.89 units on a scale STANDARD_DEVIATION 5.59 | 18.33 units on a scale STANDARD_DEVIATION 7.64 | 19.32 units on a scale STANDARD_DEVIATION 8 |
| PGA (Physician's Global Assessment) | 3.28 units on a scale STANDARD_DEVIATION 0.6 | 3.36 units on a scale STANDARD_DEVIATION 0.56 | 3.22 units on a scale STANDARD_DEVIATION 0.59 | 3.27 units on a scale STANDARD_DEVIATION 0.66 |
| Psoriasis Duration | 16.7 years STANDARD_DEVIATION 13.94 | 14.94 years STANDARD_DEVIATION 14.73 | 19.29 years STANDARD_DEVIATION 13.59 | 15.87 years STANDARD_DEVIATION 13.55 |
| Psoriatic Arthritis | 9 Participants | 4 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 1 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 3 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 2 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 77 Participants | 27 Participants | 24 Participants | 26 Participants |
| Sex: Female, Male Female | 30 Participants | 9 Participants | 11 Participants | 10 Participants |
| Sex: Female, Male Male | 67 Participants | 24 Participants | 20 Participants | 23 Participants |
| Statin Use | 8 Participants | 1 Participants | 4 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 33 | 15 / 31 | 33 / 33 |
| serious Total, serious adverse events | 2 / 33 | 0 / 31 | 0 / 33 |
Outcome results
Primary
Change in Cardiometabolic Biomarkers: Cholesterol Efflux
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on cholesterol efflux capacity. The ability to promote cholesterol efflux from macrophages is a classic function of HDL that is thought to be an important mechanism by which HDL protects against atherosclerosis. HDL cholesterol efflux capacity assays are performed based on published methods using J774 cells derived from a murine macrophage cell line (Mehta NN Atherosclerosis 2012). Efflux is calculated as a unitless measure by using the following formula: \[(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)\]. The pooled plasma was obtained from five healthy volunteers.
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Cardiometabolic Biomarkers: Cholesterol Efflux | 0.05 unitless | Standard Deviation 0.25 |
| Placebo Injection | Change in Cardiometabolic Biomarkers: Cholesterol Efflux | 0.00 unitless | Standard Deviation 0.15 |
| NB-UVB Phototherapy | Change in Cardiometabolic Biomarkers: Cholesterol Efflux | 0.04 unitless | Standard Deviation 0.16 |
p-value: 0.357Regression, Linear
p-value: 0.496Regression, Linear
Primary
Change in Cardiometabolic Biomarkers: GlycA
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on GlycA
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Cardiometabolic Biomarkers: GlycA | -35.89 log(pg/mL) | Standard Deviation 40.38 |
| Placebo Injection | Change in Cardiometabolic Biomarkers: GlycA | 5.28 log(pg/mL) | Standard Deviation 66.83 |
| NB-UVB Phototherapy | Change in Cardiometabolic Biomarkers: GlycA | -1.92 log(pg/mL) | Standard Deviation 52.89 |
p-value: 0.006Regression, Linear
p-value: 0.628Regression, Linear
Primary
Change in Cardiometabolic Biomarkers: High Density Lipoprotein Particle Total
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on high density lipoprotein particle total.
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Cardiometabolic Biomarkers: High Density Lipoprotein Particle Total | 0.59 umol/L | Standard Deviation 4 |
| Placebo Injection | Change in Cardiometabolic Biomarkers: High Density Lipoprotein Particle Total | -1.97 umol/L | Standard Deviation 7.03 |
| NB-UVB Phototherapy | Change in Cardiometabolic Biomarkers: High Density Lipoprotein Particle Total | 1.35 umol/L | Standard Deviation 5.06 |
p-value: 0.089Regression, Linear
p-value: 0.03Regression, Linear
Primary
Change in Cardiometabolic Biomarkers: Log Adiponectin
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log adiponectin.
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Cardiometabolic Biomarkers: Log Adiponectin | -0.07 log(ug/mL) | Standard Deviation 2.05 |
| Placebo Injection | Change in Cardiometabolic Biomarkers: Log Adiponectin | 0.07 log(ug/mL) | Standard Deviation 0.45 |
| NB-UVB Phototherapy | Change in Cardiometabolic Biomarkers: Log Adiponectin | -0.08 log(ug/mL) | Standard Deviation 0.41 |
p-value: 0.672Regression, Linear
p-value: 0.655Regression, Linear
Primary
Change in Cardiometabolic Biomarkers: Log C-reactive Protein
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log C-reactive protein (CRP).
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Cardiometabolic Biomarkers: Log C-reactive Protein | -0.52 log(pg/mL) | Standard Deviation 1 |
| Placebo Injection | Change in Cardiometabolic Biomarkers: Log C-reactive Protein | 0.35 log(pg/mL) | Standard Deviation 1.06 |
| NB-UVB Phototherapy | Change in Cardiometabolic Biomarkers: Log C-reactive Protein | -0.50 log(pg/mL) | Standard Deviation 1.14 |
p-value: 0.002Regression, Linear
p-value: 0.009Regression, Linear
Primary
Change in Cardiometabolic Biomarkers: Log Insulin
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log insulin.
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Cardiometabolic Biomarkers: Log Insulin | -0.19 log(pg/mL) | Standard Deviation 0.71 |
| Placebo Injection | Change in Cardiometabolic Biomarkers: Log Insulin | -0.21 log(pg/mL) | Standard Deviation 0.74 |
| NB-UVB Phototherapy | Change in Cardiometabolic Biomarkers: Log Insulin | -0.13 log(pg/mL) | Standard Deviation 0.46 |
p-value: 0.934Regression, Linear
p-value: 0.679Regression, Linear
Primary
Change in Cardiometabolic Biomarkers: Log Interleukin 6
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log interleukin 6.
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Cardiometabolic Biomarkers: Log Interleukin 6 | -0.57 log(pg/mL) | Standard Deviation 1.08 |
| Placebo Injection | Change in Cardiometabolic Biomarkers: Log Interleukin 6 | 0.20 log(pg/mL) | Standard Deviation 0.99 |
| NB-UVB Phototherapy | Change in Cardiometabolic Biomarkers: Log Interleukin 6 | -0.49 log(pg/mL) | Standard Deviation 1.08 |
p-value: 0.007Regression, Linear
p-value: 0.019Regression, Linear
Primary
Change in Cardiometabolic Biomarkers: Log Leptin
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log leptin.
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Cardiometabolic Biomarkers: Log Leptin | -0.06 log(pg/mL) | Standard Deviation 0.55 |
| Placebo Injection | Change in Cardiometabolic Biomarkers: Log Leptin | 0.03 log(pg/mL) | Standard Deviation 0.47 |
| NB-UVB Phototherapy | Change in Cardiometabolic Biomarkers: Log Leptin | 0.08 log(pg/mL) | Standard Deviation 0.42 |
p-value: 0.504Regression, Linear
p-value: 0.695Regression, Linear
Primary
Change in Cardiometabolic Biomarkers: Log Tumor Necrosis Factor-alpha
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log Tumor necrosis factor-alpha.
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Cardiometabolic Biomarkers: Log Tumor Necrosis Factor-alpha | -0.27 log(pg/mL) | Standard Deviation 0.33 |
| Placebo Injection | Change in Cardiometabolic Biomarkers: Log Tumor Necrosis Factor-alpha | 0.14 log(pg/mL) | Standard Deviation 0.38 |
| NB-UVB Phototherapy | Change in Cardiometabolic Biomarkers: Log Tumor Necrosis Factor-alpha | -0.04 log(pg/mL) | Standard Deviation 0.36 |
p-value: <0.001Regression, Linear
p-value: 0.065Regression, Linear
Primary
Change in Cardiometabolic Biomarkers: Low Density Lipoprotein Particle Total
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on low density lipoprotein particle total.
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Cardiometabolic Biomarkers: Low Density Lipoprotein Particle Total | -25.70 nmol/L | Standard Deviation 263.32 |
| Placebo Injection | Change in Cardiometabolic Biomarkers: Low Density Lipoprotein Particle Total | -34.90 nmol/L | Standard Deviation 319.42 |
| NB-UVB Phototherapy | Change in Cardiometabolic Biomarkers: Low Density Lipoprotein Particle Total | 17.42 nmol/L | Standard Deviation 187.63 |
p-value: 0.897Regression, Linear
p-value: 0.467Regression, Linear
Primary
Change in Cardiometabolic Biomarkers: Total Cholesterol
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on total cholesterol.
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Cardiometabolic Biomarkers: Total Cholesterol | 1.48 mg/dL | Standard Deviation 21.25 |
| Placebo Injection | Change in Cardiometabolic Biomarkers: Total Cholesterol | 5.00 mg/dL | Standard Deviation 25.22 |
| NB-UVB Phototherapy | Change in Cardiometabolic Biomarkers: Total Cholesterol | 3.15 mg/dL | Standard Deviation 32.81 |
p-value: 0.386Regression, Linear
p-value: 0.28Regression, Linear
Primary
Change in Vascular Inflammation
Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between baseline and week 12. The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUV mean yielding a target to background ratio (TBR).
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Vascular Inflammation | -.067 Tissue-to-background ratio (TBR) | Standard Deviation 0.213 |
| Placebo Injection | Change in Vascular Inflammation | -.052 Tissue-to-background ratio (TBR) | Standard Deviation 0.112 |
| NB-UVB Phototherapy | Change in Vascular Inflammation | -.079 Tissue-to-background ratio (TBR) | Standard Deviation 0.02 |
p-value: 0.795Regression, Linear
p-value: 0.647Regression, Linear
Secondary
Change in Patient-reported Outcomes-Dermatology Life Quality Index (DLQI)
Patient reported quality of life outcomes will be assessed using DLQI. The DLQI is calculated by summing the score of 10 questions regarding impact of skin condition on daily life resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.
Time frame: Baseline - Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Patient-reported Outcomes-Dermatology Life Quality Index (DLQI) | -7.91 units on a scale | Standard Deviation 8.77 |
| Placebo Injection | Change in Patient-reported Outcomes-Dermatology Life Quality Index (DLQI) | -3.73 units on a scale | Standard Deviation 8 |
| NB-UVB Phototherapy | Change in Patient-reported Outcomes-Dermatology Life Quality Index (DLQI) | -9.27 units on a scale | Standard Deviation 4.7 |
Secondary
Change in Patient-reported Outcomes-EuroQol EQ-5D
EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ VAS. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression on a scale ranging from 1 (no health state problem) to 3 (extreme health state problems). The EQ VAS records the patient's self-rated health on a vertical visual analogue scale ranging from 0, worst health state, to 100, best health state. A scoring function is used to assign a value (i.e., EQ-5D™ index score) to self-reported health states from a set of population-based preference weights. For the U.S. general population, the possible EQ-5D index scores range from -0.11 to 1.0 where 0.0 = death and 1.0 = perfect health.
Time frame: Baseline -Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Patient-reported Outcomes-EuroQol EQ-5D | .07 units on a scale | Standard Deviation 0.14 |
| Placebo Injection | Change in Patient-reported Outcomes-EuroQol EQ-5D | .0 units on a scale | Standard Deviation 0.17 |
| NB-UVB Phototherapy | Change in Patient-reported Outcomes-EuroQol EQ-5D | .16 units on a scale | Standard Deviation 0.19 |
Secondary
Change in Patient-reported Outcomes-International Physical Activity Questionnaire (IPAQ)
Patient reported physical activity will be assessed using IPAQ. IPAQ is an instrument designed primarily for population surveillance of physical activity among adults with activity measured in metabolic equivalent (MET)-minutes per week.
Time frame: Baseline week 4, 8 and 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Patient-reported Outcomes-International Physical Activity Questionnaire (IPAQ) | 1282 MET-minutes/week | Standard Deviation 4837 |
| Placebo Injection | Change in Patient-reported Outcomes-International Physical Activity Questionnaire (IPAQ) | 141 MET-minutes/week | Standard Deviation 2921 |
| NB-UVB Phototherapy | Change in Patient-reported Outcomes-International Physical Activity Questionnaire (IPAQ) | 18 MET-minutes/week | Standard Deviation 2994 |
Secondary
Change in Patient-reported Outcomes-MEDFICTS Dietary Assessment)
Patient reported dietary outcomes will be assessed using MEDFICTS (Meats, Eggs, Dairy, Fried foods, fat In baked goods, Convenience foods, fats added at the Table, and Snacks), a brief dietary assessment instrument for properly assessing cardiovascular diet. The questionnaire yields a continuous score (ranging from 0 to 216), with a score of \<40 indicating adherence to the Therapeutic Lifestyle Changes (TLC) diet (intake of \<7% of energy from saturated fat, \<30% of energy from total fat, and \<200 mg dietary cholesterol/day).
Time frame: Baseline to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab (Humira) | Change in Patient-reported Outcomes-MEDFICTS Dietary Assessment) | -10.17 units on a scale | Standard Deviation 17.47 |
| Placebo Injection | Change in Patient-reported Outcomes-MEDFICTS Dietary Assessment) | -13.66 units on a scale | Standard Deviation 28.59 |
| NB-UVB Phototherapy | Change in Patient-reported Outcomes-MEDFICTS Dietary Assessment) | -16.29 units on a scale | Standard Deviation 20.94 |
Secondary
Change in Psoriasis Activity (PASI-75 and PGA)
Psoriasis activity will be assessed using standard psoriasis measurements, PASI75 and PGA Clear/Almost Clear
Time frame: Baseline - Week 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adalimumab (Humira) | Change in Psoriasis Activity (PASI-75 and PGA) | PASI75 | 15 Participants |
| Adalimumab (Humira) | Change in Psoriasis Activity (PASI-75 and PGA) | PGA Clear/Almost Clear | 14 Participants |
| Placebo Injection | Change in Psoriasis Activity (PASI-75 and PGA) | PASI75 | 2 Participants |
| Placebo Injection | Change in Psoriasis Activity (PASI-75 and PGA) | PGA Clear/Almost Clear | 2 Participants |
| NB-UVB Phototherapy | Change in Psoriasis Activity (PASI-75 and PGA) | PASI75 | 14 Participants |
| NB-UVB Phototherapy | Change in Psoriasis Activity (PASI-75 and PGA) | PGA Clear/Almost Clear | 8 Participants |
Secondary
Number of Patients With Adverse Events.
Safety will be assessed by comparing how many patients have adverse events depending on whether they are on adalimumab, as compared to NB-UVB phototherapy or placebo.
Time frame: Baseline - Week 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adalimumab (Humira) | Number of Patients With Adverse Events. | pruritis | 0 Participants |
| Adalimumab (Humira) | Number of Patients With Adverse Events. | headache | 1 Participants |
| Adalimumab (Humira) | Number of Patients With Adverse Events. | nasal congestion | 1 Participants |
| Adalimumab (Humira) | Number of Patients With Adverse Events. | erythema | 0 Participants |
| Adalimumab (Humira) | Number of Patients With Adverse Events. | sore throat | 0 Participants |
| Adalimumab (Humira) | Number of Patients With Adverse Events. | cough | 0 Participants |
| Adalimumab (Humira) | Number of Patients With Adverse Events. | tooth infection | 0 Participants |
| Adalimumab (Humira) | Number of Patients With Adverse Events. | joint range of motion decrease | 2 Participants |
| Adalimumab (Humira) | Number of Patients With Adverse Events. | photosensitivity | 0 Participants |
| Adalimumab (Humira) | Number of Patients With Adverse Events. | depression | 0 Participants |
| Adalimumab (Humira) | Number of Patients With Adverse Events. | myalgia | 0 Participants |
| Adalimumab (Humira) | Number of Patients With Adverse Events. | upper respiratory infection | 3 Participants |
| Placebo Injection | Number of Patients With Adverse Events. | cough | 2 Participants |
| Placebo Injection | Number of Patients With Adverse Events. | tooth infection | 2 Participants |
| Placebo Injection | Number of Patients With Adverse Events. | erythema | 0 Participants |
| Placebo Injection | Number of Patients With Adverse Events. | pruritis | 0 Participants |
| Placebo Injection | Number of Patients With Adverse Events. | photosensitivity | 0 Participants |
| Placebo Injection | Number of Patients With Adverse Events. | upper respiratory infection | 4 Participants |
| Placebo Injection | Number of Patients With Adverse Events. | nasal congestion | 1 Participants |
| Placebo Injection | Number of Patients With Adverse Events. | sore throat | 2 Participants |
| Placebo Injection | Number of Patients With Adverse Events. | headache | 2 Participants |
| Placebo Injection | Number of Patients With Adverse Events. | myalgia | 2 Participants |
| Placebo Injection | Number of Patients With Adverse Events. | joint range of motion decrease | 0 Participants |
| Placebo Injection | Number of Patients With Adverse Events. | depression | 0 Participants |
| NB-UVB Phototherapy | Number of Patients With Adverse Events. | erythema | 14 Participants |
| NB-UVB Phototherapy | Number of Patients With Adverse Events. | headache | 2 Participants |
| NB-UVB Phototherapy | Number of Patients With Adverse Events. | photosensitivity | 3 Participants |
| NB-UVB Phototherapy | Number of Patients With Adverse Events. | tooth infection | 0 Participants |
| NB-UVB Phototherapy | Number of Patients With Adverse Events. | myalgia | 1 Participants |
| NB-UVB Phototherapy | Number of Patients With Adverse Events. | pruritis | 6 Participants |
| NB-UVB Phototherapy | Number of Patients With Adverse Events. | depression | 2 Participants |
| NB-UVB Phototherapy | Number of Patients With Adverse Events. | cough | 0 Participants |
| NB-UVB Phototherapy | Number of Patients With Adverse Events. | nasal congestion | 2 Participants |
| NB-UVB Phototherapy | Number of Patients With Adverse Events. | joint range of motion decrease | 0 Participants |
| NB-UVB Phototherapy | Number of Patients With Adverse Events. | sore throat | 1 Participants |
| NB-UVB Phototherapy | Number of Patients With Adverse Events. | upper respiratory infection | 2 Participants |