Cardiovascular Disease, Psoriasis
Conditions
Keywords
Psoriasis, Cardiovascular Disease, Vascular Inflammation, Lipid Biomarkers, FDG-PET/CT
Brief summary
The VIP-U Study is a clinical trial designed to investigate the effect of ustekinumab (Stelara) and placebo on reducing vascular inflammation and cardiometabolic risk biomarkers in patients with moderate to severe psoriasis. This study will look for systemic vascular inflammation in study participants with a test called FDG PET/CT (fluorodeoxyglucose-positron emission tomography/computed tomography). The study will also look for cardiometabolic identifiers (heart disease and metabolic factors) in blood samples, including markers of high cholesterol, cholesterol efflux function (the ability of cholesterol to move in the body), metabolic factors, and inflammation. The study will also examine the effects of ustekinumab compared to placebo on psoriasis activity, severity and safety.
Interventions
DRUGUstekinumab
DRUGPlacebo
Sponsors
Janssen Scientific Affairs, LLC
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
A hybrid RCT (randomized controlled trial) crossover trial where all patients receive total of 52 weeks of active treatment following an RCT phase of 12 weeks (active treatment or placebo). Patients randomized to active treatment will receive additional 40 weeks of active treatment at end of RCT phase; patients randomized to placebo will receive 52 weeks of active treatment at end of RCT phase. Primary outcomes are assessed at end of the RCT phase (comparison of interventions in change from start of treatment) and at end of 52 weeks of active treatment (change from start of treatment).
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 score of ≥ 12 at the Baseline (Week 0) visit. 6. Subject is a candidate for systemic therapy 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 periodic pregnancy testing during the study and agree to use at least one method of contraception throughout the study duration and for at least 15 weeks after the last dose of the study drug 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. 8. Men are eligible to participate in the study if they meet one of the following criteria: 1. Agree to use a proven birth control method during the study and for at least 15 weeks after the last dose of the study drug. 2. Have a female partner who agrees to use at least one method of contraception throughout the study duration and for at least 15 weeks after the last dose of the study drug. 3. Have a female partner who is postmenopausal (for at least one year), sterile, or hysterectomized; 4. Have a female partner who has undergone tubal ligation, 5. Agree to be sexually abstinent, defined as total abstinence from sexual intercourse, as a form of contraception. 9. 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. 10. 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 an IL-12/IL-23 antagonist that led to discontinuation of therapy and contraindicates future treatment. 2. Previous lack of response to an IL-12/IL-23 antagonist that led to discontinuation of therapy. 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 or Excimer laser for at least 14 days prior to the Baseline (Week 0) visit and during the study. 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 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). * Any IL-12/IL-23 antagonist (e.g., ustekinumab, briakinumab) 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, cerebrovascular accident or myocardial infarction within the prior 6 months, 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 with the exception 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. 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 positive Quantiferon-GOLD result; 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 within 3 years prior to the first administration of study agent. * Any other significant infection requiring hospitalization or intravenous (IV) antibiotics in the month prior to Baseline; * Infection requiring treatment with oral or parenteral (other than IV) antibiotics within 14 days prior to Baseline; * Subject has received vaccination with Bacille Calmette-Guerin (BCG) within 365 days prior to Screening or will receive BCG vaccination during study participation including up to 12 months after the last dose of the study drug; * 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 3 months after the last dose of study drug. 13. Subject has history of hematological or solid malignancy within the past five years other than successfully treated basal cell carcinoma, non-metastatic cutaneous squamous cell carcinoma or cervical carcinoma in situ. 14. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study. 15. Male subject who is considering fathering a child 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 109/L and absolute neutrophil count (ANC) is \>1000 cells / mm3. * WBC count \> 15 x 109/L; * Platelet count \< 100 x 109/L; * Serum creatinine \>1.6 mg/dL (\>141 µmol/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) 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Metabolic Biomarker Levels: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on HOMA-IR, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). HOMA-IR, a method used to quantify insulin resistance and beta-cell function, is expressed using fasting blood glucose and insulin levels. It is calculated using the formula (HOMA-IR = fasting glucose \[mg/dl\] \* fasting insulin \[mU/ml\]/405). |
| Change in Lipid Biomarker Levels: Fetuin-A | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Fetuin-A, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Metabolic Biomarker Levels: Adiponectin | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Adiponectin, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Metabolic Biomarker Levels: Leptin | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Leptin, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Metabolic Biomarker Levels: Insulin | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Insulin, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Metabolic Biomarker Levels: Glucose | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Glucose, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Vascular Inflammation | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between baseline and week 12 (RCT period) or end of study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). 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 Inflammatory Biomarker Levels: Intercellular Adhesion Molecule-1 (ICAM-1) | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on ICAM-1, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: Vascular Cell Adhesion Molecule-1 (VCAM-1) | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on VCAM-1, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: C-reactive Protein (CRP) | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on CRP, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: Ferritin | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Ferritin, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: Serum Amyloid A (SAA) | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on SAA, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: Interferon-gamma (INF-g) | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on INF-g,, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: Monocyte Chemoattractant Protein-1 (MCP-1) | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on MCP-1, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: Tumor Necrosis Factor-alpha (TNF-a) | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on TNF-a, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: GlycA | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on GlycA, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: Interleukin (IL)-1b | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-1b, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: IL-2ra | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-2ra, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: IL-12/23 | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-12/23, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: IL-17a | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-17a, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: IL-18 | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-18, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: IL-6 | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-6, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Inflammatory Biomarker Levels: IL-8 | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-8, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Triglycerides | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Triglycerides, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Total Cholesterol | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Total cholesterol, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: High-density Lipoprotein (HDL) Cholesterol | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on HDL cholesterol, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: HDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: HDL Particle Size | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on HDL particle size, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Large-HDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large-HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Small-HDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Small-HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Medium-HDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Medium-HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Large Medium-HDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large medium-HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Low-density Lipoprotein (LDL) Cholesterol | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on LDL cholesterol, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: LDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on LDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: LDL Particle Size | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on LDL particle size, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Small-LDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Small-LDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Large-LDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large-LDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Very Large-LDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Very large-LDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Very Low-density Lipoprotein (VLDL) Particle Size | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on VLDL particle size, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: VLDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: VLDL Triglycerides | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on VLDL triglycerides, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Small-VLDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Small-VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Medium-VLDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Medium-VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Large Medium-VLDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large medium-VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Large-VLDL Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large-VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Intermediate-density Lipoprotein (IDL) Particle Number | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
| Change in Lipid Biomarker Levels: Cholesterol Efflux Capacity | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Cholesterol efflux capacity, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). 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: \[(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)\]. |
| Change in Lipid Biomarker Levels: Apolipoprotein-B | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Apolipoprotein-B, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving PASI90 (90% or Greater Reduction in PASI Score) | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on PASI90, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). Binary measure of change in psoriasis activity; 90% or greater reduction in PASI score compared to baseline. |
| Number of Participants Achieving Physician Global Assessment (PGA) Clear/Almost Clear | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on PGA clear/almost clear, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). Binary measure of psoriasis disease activity at measurement time points; Physician Global Assessment score \<1.5 (clear/almost clear) |
| Change in Patient-Reported Outcomes: MEDFICTS | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on MEDFICTS, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). MEDFICTS (Meats, Eggs, Dairy, Fried foods, fat In baked goods, Convenience foods, fats added at the Table, and Snacks), a brief dietary assessment instrument, has been provided as part of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) guidelines as a free tool to use for proper cardiovascular diet assessment. 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 Physical Activity Assessments: IPAQ | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IPAQ, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). 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 Participants Achieving PASI75 (75% or Greater Reduction in PASI Score) | Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) | To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on PASI75, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). Binary measure of change in psoriasis activity; 75% or greater reduction in PASI score compared to baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ustekinumab (Stelara) Ustekinumab (Stelara) subcutaneous injection 45mg (if person's weight is 100kg or less) or 90mg (if person's weight is greater than 100kg) at day 0 and week 4 followed by every 12-week dosing thereafter.
Ustekinumab | 22 |
| Placebo Placebo subcutaneous injection will be given according to the same dose and schedule as the active comparator.
Ustekinumab
Placebo | 21 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Physician Decision | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Ustekinumab (Stelara) |
|---|---|---|---|
| Age at PsA diagnosis | 40 years STANDARD_DEVIATION 15.56 | 43.6 years STANDARD_DEVIATION 14.33 | 22 years STANDARD_DEVIATION 0 |
| Age, Continuous | 42.33 years STANDARD_DEVIATION 13.38 | 45.33 years STANDARD_DEVIATION 12.76 | 39.45 years STANDARD_DEVIATION 13.6 |
| Body Mass Index | 33.28 kg/m^2 STANDARD_DEVIATION 7.1 | 33.32 kg/m^2 STANDARD_DEVIATION 6.29 | 33.24 kg/m^2 STANDARD_DEVIATION 7.95 |
| Body Surface Area (BSA) | 24.98 percentage of total body surface area STANDARD_DEVIATION 16.45 | 23.71 percentage of total body surface area STANDARD_DEVIATION 15.58 | 26.18 percentage of total body surface area STANDARD_DEVIATION 17.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 19 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Medical History Arthritis | 1 participants | 1 participants | 0 participants |
| Medical History Coronary Artery Disease | 2 participants | 1 participants | 1 participants |
| Medical History Depression | 4 participants | 2 participants | 2 participants |
| Medical History Diabetes | 1 participants | 1 participants | 0 participants |
| Medical History Hyperlipidemia | 7 participants | 2 participants | 5 participants |
| Medical History Statin Use | 6 participants | 3 participants | 3 participants |
| Medical History Stroke | 1 participants | 0 participants | 1 participants |
| Physician Global Assessment (PGA) | 3.44 calculated score STANDARD_DEVIATION 0.69 | 3.38 calculated score STANDARD_DEVIATION 0.8 | 3.5 calculated score STANDARD_DEVIATION 0.57 |
| Psoriasis Area Severity Index (PASI) score | 19.93 composite score STANDARD_DEVIATION 7.46 | 19.82 composite score STANDARD_DEVIATION 7.64 | 20.03 composite score STANDARD_DEVIATION 7.47 |
| Psoriasis duration | 18.13 years STANDARD_DEVIATION 12.58 | 20.29 years STANDARD_DEVIATION 14.41 | 16.45 years STANDARD_DEVIATION 11.02 |
| Psoriasis treatment history Biologics | 19 participants | 9 participants | 10 participants |
| Psoriasis treatment history Phototherapy | 19 participants | 9 participants | 10 participants |
| Psoriasis treatment history Systemics | 8 participants | 2 participants | 6 participants |
| Psoriatic Arthritis (PsA) present | 7 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 31 Participants | 12 Participants | 19 Participants |
| Sex: Female, Male Female | 13 Participants | 7 Participants | 6 Participants |
| Sex: Female, Male Male | 30 Participants | 14 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 21 | 0 / 19 |
| other Total, other adverse events | 14 / 22 | 3 / 21 | 16 / 19 |
| serious Total, serious adverse events | 0 / 22 | 0 / 21 | 3 / 19 |
Outcome results
Primary
Change in Inflammatory Biomarker Levels: C-reactive Protein (CRP)
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on CRP, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: C-reactive Protein (CRP) | -2886.57 ng/mL | Standard Error 2851.16 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: C-reactive Protein (CRP) | 140.64 ng/mL | Standard Error 1108.54 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: C-reactive Protein (CRP) | -1974.63 ng/mL | Standard Error 1659.11 |
Comparison: Comparison during RCT periodp-value: 0.347295% CI: [-9465.95, 3411.54]Regression, Linear
Comparison: Combined ustekinumab and placebo groups for active treatment period analysis.p-value: 0.241695% CI: [-5336.3, 1387.04]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: Ferritin
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Ferritin, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: Ferritin | -12.32 ng/mL | Standard Error 39.16 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: Ferritin | -32.97 ng/mL | Standard Error 27.4 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: Ferritin | 47.00 ng/mL | Standard Error 35.84 |
Comparison: Comparison during RCT periodp-value: 0.674295% CI: [-78.03, 119.34]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.197995% CI: [-25.63, 11963]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: GlycA
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on GlycA, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: GlycA | -0.70 umol/L | Standard Error 7.42 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: GlycA | 3.44 umol/L | Standard Error 8.76 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: GlycA | -8.35 umol/L | Standard Error 8.41 |
Comparison: Comparison during RCT periodp-value: 0.718595% CI: [-27.24, 18.96]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.327195% CI: [-25.4, 8.69]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: IL-12/23
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-12/23, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: IL-12/23 | 196.84 pg/mL | Standard Error 43.59 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: IL-12/23 | 5.35 pg/mL | Standard Error 4.63 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: IL-12/23 | 171.21 pg/mL | Standard Error 20.3 |
Comparison: Comparison during RCT periodp-value: 0.000295% CI: [98.18, 284.81]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: <0.000195% CI: [130.08, 212.34]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: IL-17a
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-17a, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: IL-17a | -1.46 pg/mL | Standard Error 0.39 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: IL-17a | 1.17 pg/mL | Standard Error 0.94 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: IL-17a | -1.15 pg/mL | Standard Error 0.32 |
Comparison: Comparison during RCT periodp-value: 0.01195% CI: [-4.62, -0.64]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.000895% CI: [-1.79, -0.51]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: IL-18
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-18, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: IL-18 | 301.21 pg/mL | Standard Error 483.77 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: IL-18 | 456.52 pg/mL | Standard Error 487.49 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: IL-18 | -407.43 pg/mL | Standard Error 180.7 |
Comparison: Comparison during RCT periodp-value: 0.822795% CI: [-1548.66, 1238.04]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.030295% CI: [-773.57, -41.29]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: IL-2ra
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-2ra, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: IL-2ra | -79.07 ng/mL | Standard Error 28.51 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: IL-2ra | -8.31 ng/mL | Standard Error 15.48 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: IL-2ra | 71.72 ng/mL | Standard Error 132.87 |
Comparison: Comparison during RCT periodp-value: 0.040895% CI: [-138.42, -3.11]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.592695% CI: [-197.5, 340.93]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: IL-6
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-6, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: IL-6 | -0.45 pg/mL | Standard Error 0.22 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: IL-6 | 0.02 pg/mL | Standard Error 0.33 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: IL-6 | -0.38 pg/mL | Standard Error 0.21 |
Comparison: Comparison during RCT periodp-value: 0.233395% CI: [-1.25, 0.32]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.071395% CI: [-0.8, 0.03]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: IL-8
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-8, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: IL-8 | 2.46 pg/mL | Standard Error 3.35 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: IL-8 | 19.33 pg/mL | Standard Error 16.02 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: IL-8 | -2.23 pg/mL | Standard Error 1.71 |
Comparison: Comparison during RCT periodp-value: 0.286995% CI: [-48.48, 14.75]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.198895% CI: [-5.69, 1.22]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: Intercellular Adhesion Molecule-1 (ICAM-1)
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on ICAM-1, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: Intercellular Adhesion Molecule-1 (ICAM-1) | 10.83 ng/mL | Standard Error 26.3 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: Intercellular Adhesion Molecule-1 (ICAM-1) | 75.80 ng/mL | Standard Error 37.19 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: Intercellular Adhesion Molecule-1 (ICAM-1) | 6.65 ng/mL | Standard Error 22.24 |
Comparison: Comparison during RCT periodp-value: 0.115995% CI: [-115.83, 25.89]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.766695% CI: [-38.41, 51.72]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: Interferon-gamma (INF-g)
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on INF-g,, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: Interferon-gamma (INF-g) | -0.03 pg/mL | Standard Error 2.25 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: Interferon-gamma (INF-g) | 0.04 pg/mL | Standard Error 0.95 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: Interferon-gamma (INF-g) | -1.09 pg/mL | Standard Error 1.09 |
Comparison: Comparison during RCT periodp-value: 0.976795% CI: [-5.22, 5.07]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.320595% CI: [-3.29, 1.11]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: Interleukin (IL)-1b
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-1b, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: Interleukin (IL)-1b | 0.07 pg/mL | Standard Error 0.38 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: Interleukin (IL)-1b | 0.60 pg/mL | Standard Error 0.34 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: Interleukin (IL)-1b | -0.31 pg/mL | Standard Error 0.11 |
Comparison: Comparison during RCT periodp-value: 0.312495% CI: [-1.56, 0.51]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.010695% CI: [-0.54, -0.08]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: Monocyte Chemoattractant Protein-1 (MCP-1)
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on MCP-1, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: Monocyte Chemoattractant Protein-1 (MCP-1) | -14.66 pg/mL | Standard Error 15.51 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: Monocyte Chemoattractant Protein-1 (MCP-1) | 0.13 pg/mL | Standard Error 12.09 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: Monocyte Chemoattractant Protein-1 (MCP-1) | -7.24 pg/mL | Standard Error 11.47 |
Comparison: Comparison during RCT periodp-value: 0.463295% CI: [-55.19, 25.61]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.531695% CI: [-30.47, 15.99]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: Serum Amyloid A (SAA)
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on SAA, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: Serum Amyloid A (SAA) | -7687.80 ng/mL | Standard Error 7389 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: Serum Amyloid A (SAA) | 196.49 ng/mL | Standard Error 203.34 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: Serum Amyloid A (SAA) | -3782.54 ng/mL | Standard Error 4073.25 |
Comparison: Comparison during RCT periodp-value: 0.317395% CI: [-23634.67, 7566.1]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.359195% CI: [-12035.72, 4470.64]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: Tumor Necrosis Factor-alpha (TNF-a)
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on TNF-a, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: Tumor Necrosis Factor-alpha (TNF-a) | -0.22 pg/mL | Standard Error 0.51 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: Tumor Necrosis Factor-alpha (TNF-a) | 0.68 pg/mL | Standard Error 0.44 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: Tumor Necrosis Factor-alpha (TNF-a) | -0.67 pg/mL | Standard Error 0.34 |
Comparison: Comparison during RCT periodp-value: 0.192895% CI: [-2.27, 0.47]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.05895% CI: [-1.36, 0.02]Regression, Linear
Primary
Change in Inflammatory Biomarker Levels: Vascular Cell Adhesion Molecule-1 (VCAM-1)
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on VCAM-1, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Inflammatory Biomarker Levels: Vascular Cell Adhesion Molecule-1 (VCAM-1) | -20.36 ng/mL | Standard Error 18.39 |
| Placebo (RCT Period) | Change in Inflammatory Biomarker Levels: Vascular Cell Adhesion Molecule-1 (VCAM-1) | 60.53 ng/mL | Standard Error 24.76 |
| Total (Active Treatment Period) | Change in Inflammatory Biomarker Levels: Vascular Cell Adhesion Molecule-1 (VCAM-1) | -1.99 ng/mL | Standard Error 14.11 |
Comparison: Comparison during RCT periodp-value: 0.011595% CI: [-142.55, -19.23]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.888395% CI: [-30.58, 26.59]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Apolipoprotein-B
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Apolipoprotein-B, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Apolipoprotein-B | 0.11 ug/mL | Standard Error 0.09 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Apolipoprotein-B | -0.04 ug/mL | Standard Error 0.09 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Apolipoprotein-B | 0.10 ug/mL | Standard Error 0.06 |
p-value: 0.245395% CI: [-0.11, 0.41]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.108795% CI: [-0.02, 0.23]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Cholesterol Efflux Capacity
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Cholesterol efflux capacity, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). 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: \[(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)\].
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Cholesterol Efflux Capacity | 0.09 unitless (see description) | Standard Error 0.03 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Cholesterol Efflux Capacity | 0.03 unitless (see description) | Standard Error 0.03 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Cholesterol Efflux Capacity | 0.04 unitless (see description) | Standard Error 0.03 |
Comparison: Comparison during RCT periodp-value: 0.179295% CI: [-0.03, 0.14]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.255995% CI: [-0.03, 0.1]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Fetuin-A
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Fetuin-A, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Fetuin-A | 10.22 ug/mL | Standard Error 29.47 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Fetuin-A | -38.21 ug/mL | Standard Error 56.05 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Fetuin-A | -49.56 ug/mL | Standard Error 27.84 |
Comparison: Comparison during RCT periodp-value: 0.436895% CI: [-76.31, 173.16]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.083395% CI: [-105.97, 6.85]Regression, Linear
Primary
Change in Lipid Biomarker Levels: HDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: HDL Particle Number | -0.02 nmol/L | Standard Error 0.69 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: HDL Particle Number | -1.27 nmol/L | Standard Error 0.77 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: HDL Particle Number | 0.91 nmol/L | Standard Error 0.72 |
Comparison: Comparison during RCT periodp-value: 0.230595% CI: [-0.83, 3.34]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.218995% CI: [-0.53, 2.37]Regression, Linear
Primary
Change in Lipid Biomarker Levels: HDL Particle Size
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on HDL particle size, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: HDL Particle Size | 0.08 nm | Standard Error 0.05 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: HDL Particle Size | 0.19 nm | Standard Error 0.1 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: HDL Particle Size | 0.17 nm | Standard Error 0.07 |
Comparison: Comparison during RCT periodp-value: 0.321295% CI: [-0.34, 0.11]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.013795% CI: [0.04, 0.31]Regression, Linear
Primary
Change in Lipid Biomarker Levels: High-density Lipoprotein (HDL) Cholesterol
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on HDL cholesterol, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: High-density Lipoprotein (HDL) Cholesterol | 2.24 mg/dL | Standard Error 1.31 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: High-density Lipoprotein (HDL) Cholesterol | -1.42 mg/dL | Standard Error 1.46 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: High-density Lipoprotein (HDL) Cholesterol | 1.92 mg/dL | Standard Error 1.42 |
Comparison: Comparison during RCT periodp-value: 0.069395% CI: [-0.3, 7.62]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.184195% CI: [-0.96, 4.8]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Intermediate-density Lipoprotein (IDL) Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Intermediate-density Lipoprotein (IDL) Particle Number | 50.86 nmol/L | Standard Error 25.89 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Intermediate-density Lipoprotein (IDL) Particle Number | -101.79 nmol/L | Standard Error 36.04 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Intermediate-density Lipoprotein (IDL) Particle Number | -2.97 nmol/L | Standard Error 25.7 |
Comparison: Comparison during RCT periodp-value: 0.001295% CI: [64.07, 241.23]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.908595% CI: [-55.04, 49.09]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Large-HDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large-HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Large-HDL Particle Number | 0.46 nmol/L | Standard Error 0.38 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Large-HDL Particle Number | 0.33 nmol/L | Standard Error 0.47 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Large-HDL Particle Number | 0.51 nmol/L | Standard Error 0.36 |
Comparison: Comparison during RCT periodp-value: 0.838395% CI: [-1.09, 1.33]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.165195% CI: [-0.22, 1.24]Regression, Logistic
Primary
Change in Lipid Biomarker Levels: Large-LDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large-LDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Large-LDL Particle Number | 28.95 nmol/L | Standard Error 26.87 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Large-LDL Particle Number | 21.95 nmol/L | Standard Error 41.87 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Large-LDL Particle Number | -24.76 nmol/L | Standard Error 32.59 |
Comparison: Comparison during RCT periodp-value: 0.886695% CI: [-91.8, 105.81]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.452795% CI: [-90.78, 41.3]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Large Medium-HDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large medium-HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Large Medium-HDL Particle Number | 0.02 nmol/L | Standard Error 1.26 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Large Medium-HDL Particle Number | 1.14 nmol/L | Standard Error 1.43 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Large Medium-HDL Particle Number | 0.77 nmol/L | Standard Error 1 |
Comparison: Comparison during RCT periodp-value: 0.55895% CI: [-4.95, 2.71]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.445495% CI: [-1.25, 2.8]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Large Medium-VLDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large medium-VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Large Medium-VLDL Particle Number | -2.89 nmol/L | Standard Error 3.33 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Large Medium-VLDL Particle Number | -2.97 nmol/L | Standard Error 3.98 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Large Medium-VLDL Particle Number | 0.38 nmol/L | Standard Error 2.59 |
Comparison: Comparison during RCT periodp-value: 0.98895% CI: [-10.37, 10.53]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.883695% CI: [-4.86, 5.63]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Large-VLDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large-VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Large-VLDL Particle Number | 0.29 nmol/L | Standard Error 0.86 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Large-VLDL Particle Number | 0.57 nmol/L | Standard Error 0.99 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Large-VLDL Particle Number | 2.30 nmol/L | Standard Error 1.08 |
Comparison: Comparison during RCT periodp-value: 0.832195% CI: [-2.91, 2.36]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.039495% CI: [0.12, 4.48]Regression, Linear
Primary
Change in Lipid Biomarker Levels: LDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on LDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: LDL Particle Number | 112.67 nmol/L | Standard Error 46.44 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: LDL Particle Number | -118.11 nmol/L | Standard Error 52.45 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: LDL Particle Number | -31.89 nmol/L | Standard Error 41.71 |
Comparison: Comparison during RCT periodp-value: 0.002195% CI: [89.47, 372.08]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.449395% CI: [-116.4, 52.61]Regression, Linear
Primary
Change in Lipid Biomarker Levels: LDL Particle Size
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on LDL particle size, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: LDL Particle Size | 0.20 nmol/L | Standard Error 0.11 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: LDL Particle Size | 0.15 nmol/L | Standard Error 0.13 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: LDL Particle Size | 0.03 nmol/L | Standard Error 0.11 |
Comparison: Comparison during RCT periodp-value: 0.800895% CI: [-0.3, 0.38]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.806895% CI: [-0.19, 0.24]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Low-density Lipoprotein (LDL) Cholesterol
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on LDL cholesterol, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Low-density Lipoprotein (LDL) Cholesterol | 12.52 mg/dL | Standard Error 4.21 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Low-density Lipoprotein (LDL) Cholesterol | -8.84 mg/dL | Standard Error 5.25 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Low-density Lipoprotein (LDL) Cholesterol | -2.92 mg/dL | Standard Error 4.07 |
Comparison: Comparison during RCT periodp-value: 0.002795% CI: [7.86, 34.87]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.477595% CI: [-11.17, 5.33]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Medium-HDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Medium-HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Medium-HDL Particle Number | -0.56 nmol/L | Standard Error 1.21 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Medium-HDL Particle Number | 0.81 nmol/L | Standard Error 1.17 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Medium-HDL Particle Number | 0.17 nmol/L | Standard Error 0.97 |
Comparison: Comparison during RCT periodp-value: 0.423595% CI: [-4.79, 2.05]Regression, Linear
Comparison: Comparison during RCT periodp-value: 0.865395% CI: [-1.8, 2.13]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Medium-VLDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Medium-VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Medium-VLDL Particle Number | -3.50 nmol/L | Standard Error 2.98 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Medium-VLDL Particle Number | -3.84 nmol/L | Standard Error 3.5 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Medium-VLDL Particle Number | -1.86 nmol/L | Standard Error 2.43 |
Comparison: Comparison during RCT periodp-value: 0.941595% CI: [-8.91, 9.59]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.448595% CI: [-6.77, 3.06]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Small-HDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Small-HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Small-HDL Particle Number | -0.02 nmol/L | Standard Error 1.15 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Small-HDL Particle Number | -2.52 nmol/L | Standard Error 1.25 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Small-HDL Particle Number | 0.21 nmol/L | Standard Error 0.84 |
Comparison: Comparison during RCT periodp-value: 0.150295% CI: [-0.94, 5.93]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.805495% CI: [-1.49, 1.91]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Small-LDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Small-LDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Small-LDL Particle Number | 24.36 nmol/L | Standard Error 38.72 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Small-LDL Particle Number | -22.61 nmol/L | Standard Error 40.61 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Small-LDL Particle Number | 4.68 nmol/L | Standard Error 33.85 |
Comparison: Comparison during RCT periodp-value: 0.407995% CI: [-66.65, 160.57]Regression, Logistic
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.890795% CI: [-63.91, 73.28]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Small-VLDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Small-VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Small-VLDL Particle Number | -5.84 nmol/L | Standard Error 2.72 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Small-VLDL Particle Number | 9.87 nmol/L | Standard Error 5.27 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Small-VLDL Particle Number | -0.50 nmol/L | Standard Error 2.07 |
Comparison: Comparison during RCT periodp-value: 0.009795% CI: [-27.39, -4.03]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.811995% CI: [-4.69, 3.7]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Total Cholesterol
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Total cholesterol, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Total Cholesterol | 12.57 mg/dL | Standard Error 5.04 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Total Cholesterol | -6.63 mg/dL | Standard Error 5.45 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Total Cholesterol | -0.79 mg/dL | Standard Error 4.14 |
Comparison: Comparison during RCT periodp-value: 0.013595% CI: [4.21, 34.2]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.849995% CI: [-9.19, 7.61]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Triglycerides
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Triglycerides, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Triglycerides | 0.48 mg/dL | Standard Error 9.42 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Triglycerides | -1.58 mg/dL | Standard Error 8.7 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Triglycerides | 10.55 mg/dL | Standard Error 8.26 |
Comparison: Comparison during RCT periodp-value: 0.874495% CI: [-24.09, 28.2]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.209395% CI: [-6.18, 27.29]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Very Large-LDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Very large-LDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Very Large-LDL Particle Number | 93.95 nmol/L | Standard Error 45.38 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Very Large-LDL Particle Number | -100.74 nmol/L | Standard Error 48.29 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Very Large-LDL Particle Number | -29.16 nmol/L | Standard Error 38.01 |
Comparison: Comparison during RCT periodp-value: 0.005695% CI: [60.61, 328.77]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.447895% CI: [-106.17, 47.85]Regression, Linear
Primary
Change in Lipid Biomarker Levels: Very Low-density Lipoprotein (VLDL) Particle Size
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on VLDL particle size, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: Very Low-density Lipoprotein (VLDL) Particle Size | 3.19 nmol/L | Standard Error 2.19 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: Very Low-density Lipoprotein (VLDL) Particle Size | 0.04 nmol/L | Standard Error 1.69 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: Very Low-density Lipoprotein (VLDL) Particle Size | 1.50 nmol/L | Standard Error 1.41 |
Comparison: Comparison during RCT periodp-value: 0.270495% CI: [-2.55, 8.83]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.29595% CI: [-1.36, 4.36]Regression, Linear
Primary
Change in Lipid Biomarker Levels: VLDL Particle Number
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: VLDL Particle Number | -9.32 nmol/L | Standard Error 4.85 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: VLDL Particle Number | 7.42 nmol/L | Standard Error 4.34 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: VLDL Particle Number | -0.11 nmol/L | Standard Error 3.37 |
Comparison: Comparison during RCT periodp-value: 0.014995% CI: [-30.03, -3.45]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.973495% CI: [-6.93, 6.71]Regression, Linear
Primary
Change in Lipid Biomarker Levels: VLDL Triglycerides
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on VLDL triglycerides, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Lipid Biomarker Levels: VLDL Triglycerides | -4.88 mg/dL | Standard Error 8.85 |
| Placebo (RCT Period) | Change in Lipid Biomarker Levels: VLDL Triglycerides | 4.33 mg/dL | Standard Error 7.57 |
| Total (Active Treatment Period) | Change in Lipid Biomarker Levels: VLDL Triglycerides | 11.14 mg/dL | Standard Error 7.33 |
Comparison: Comparison during RCT periodp-value: 0.438495% CI: [-33.03, 14.6]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.137395% CI: [-3.72, 25.99]Regression, Linear
Primary
Change in Metabolic Biomarker Levels: Adiponectin
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Adiponectin, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Metabolic Biomarker Levels: Adiponectin | 0.04 ug/mL | Standard Error 0.79 |
| Placebo (RCT Period) | Change in Metabolic Biomarker Levels: Adiponectin | 0.32 ug/mL | Standard Error 0.77 |
| Total (Active Treatment Period) | Change in Metabolic Biomarker Levels: Adiponectin | 0.38 ug/mL | Standard Error 0.51 |
Comparison: Comparison during RCT periodp-value: 0.803695% CI: [-2.52, 1.97]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.460895% CI: [-0.65, 1.4]Regression, Linear
Primary
Change in Metabolic Biomarker Levels: Glucose
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Glucose, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Metabolic Biomarker Levels: Glucose | 2.41 mg/dL | Standard Error 3.34 |
| Placebo (RCT Period) | Change in Metabolic Biomarker Levels: Glucose | -1.79 mg/dL | Standard Error 4.02 |
| Total (Active Treatment Period) | Change in Metabolic Biomarker Levels: Glucose | 3.41 mg/dL | Standard Error 3.43 |
Comparison: Comparison during RCT periodp-value: 0.422695% CI: [-6.28, 14.68]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.32795% CI: [-3.54, 10.36]Regression, Linear
Primary
Change in Metabolic Biomarker Levels: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on HOMA-IR, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). HOMA-IR, a method used to quantify insulin resistance and beta-cell function, is expressed using fasting blood glucose and insulin levels. It is calculated using the formula (HOMA-IR = fasting glucose \[mg/dl\] \* fasting insulin \[mU/ml\]/405).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Metabolic Biomarker Levels: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | 0.07 unitless (see description) | Standard Error 1.37 |
| Placebo (RCT Period) | Change in Metabolic Biomarker Levels: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | 0.55 unitless (see description) | Standard Error 0.49 |
| Total (Active Treatment Period) | Change in Metabolic Biomarker Levels: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | -0.07 unitless (see description) | Standard Error 0.89 |
Comparison: Comparison during RCT periodp-value: 0.750795% CI: [-3.56, 2.59]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.934895% CI: [-1.88, 1.73]Regression, Linear
Primary
Change in Metabolic Biomarker Levels: Insulin
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Insulin, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Metabolic Biomarker Levels: Insulin | 36.19 pg/mL | Standard Error 116.4 |
| Placebo (RCT Period) | Change in Metabolic Biomarker Levels: Insulin | 105.13 pg/mL | Standard Error 51.42 |
| Total (Active Treatment Period) | Change in Metabolic Biomarker Levels: Insulin | -7.96 pg/mL | Standard Error 85.98 |
Comparison: Comparison during RCT periodp-value: 0.604295% CI: [-335.97, 198.08]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.926795% CI: [-182.18, 166.26]Regression, Linear
Primary
Change in Metabolic Biomarker Levels: Leptin
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Leptin, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Metabolic Biomarker Levels: Leptin | 8022.19 pg/mL | Standard Error 2576.52 |
| Placebo (RCT Period) | Change in Metabolic Biomarker Levels: Leptin | 4701.61 pg/mL | Standard Error 2184.57 |
| Total (Active Treatment Period) | Change in Metabolic Biomarker Levels: Leptin | 6926.25 pg/mL | Standard Error 2257.84 |
Comparison: Comparison during RCT periodp-value: 0.33795% CI: [-3592.52, 10233.67]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatmentp-value: 0.00495% CI: [2351.43, 11501.07]Regression, 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 (RCT period) or end of study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). 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; Baseline - End of Study Visit (Week 52 or Week 64)
Population: The number of subjects analyzed reflect patient dropouts and availability of analyzable samples. The two arms in the RCT period are compared in Statistical Analysis 1. The composite Total group is used to assess 52 weeks of active treatment at end of study compared to baseline and is analyzed separately in Statistical Analysis 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Vascular Inflammation | -0.1015 TBR max | Standard Error 0.0465 |
| Placebo (RCT Period) | Change in Vascular Inflammation | 0.1442 TBR max | Standard Error 0.0137 |
| Total (Active Treatment Period) | Change in Vascular Inflammation | -0.0151 TBR max | Standard Error 0.0353 |
Comparison: Comparison during RCT periodp-value: 0.001295% CI: [-0.3873, -0.104]Regression, Linear
Comparison: Global change from baseline after 52 weeks of active treatment.p-value: 0.671895% CI: [-0.0867, 0.0565]Regression, Linear
Secondary
Change in Patient-Reported Outcomes: MEDFICTS
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on MEDFICTS, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). MEDFICTS (Meats, Eggs, Dairy, Fried foods, fat In baked goods, Convenience foods, fats added at the Table, and Snacks), a brief dietary assessment instrument, has been provided as part of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) guidelines as a free tool to use for proper cardiovascular diet assessment. 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 - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Patient-Reported Outcomes: MEDFICTS | -5.68 MEDFICTS score | Standard Error 3.97 |
| Placebo (RCT Period) | Change in Patient-Reported Outcomes: MEDFICTS | -14.00 MEDFICTS score | Standard Error 4.98 |
| Total (Active Treatment Period) | Change in Patient-Reported Outcomes: MEDFICTS | 8.32 MEDFICTS score | Standard Error 6.3 |
p-value: 0.194495% CI: [-4.42, 21.06]Regression, Linear
p-value: 0.001195% CI: [-19.4, -5.25]Regression, Linear
Secondary
Change in Patient-reported Physical Activity Assessments: IPAQ
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IPAQ, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). 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 12; Baseline - End of Study Visit (Week 52 or Week 64)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ustekinumab (RCT Period) | Change in Patient-reported Physical Activity Assessments: IPAQ | 73.69 MET-minutes/week | Standard Error 808.45 |
| Placebo (RCT Period) | Change in Patient-reported Physical Activity Assessments: IPAQ | 853.28 MET-minutes/week | Standard Error 562.37 |
| Total (Active Treatment Period) | Change in Patient-reported Physical Activity Assessments: IPAQ | -779.59 MET-minutes/week | Standard Error 1049.99 |
p-value: 0.462895% CI: [-2911.19, 1352.01]Regression, Linear
p-value: 0.220995% CI: [-2395.95, 574.27]Regression, Linear
Secondary
Number of Participants Achieving PASI75 (75% or Greater Reduction in PASI Score)
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on PASI75, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). Binary measure of change in psoriasis activity; 75% or greater reduction in PASI score compared to baseline.
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ustekinumab (RCT Period) | Number of Participants Achieving PASI75 (75% or Greater Reduction in PASI Score) | 17 Participants |
| Placebo (RCT Period) | Number of Participants Achieving PASI75 (75% or Greater Reduction in PASI Score) | 2 Participants |
| Total (Active Treatment Period) | Number of Participants Achieving PASI75 (75% or Greater Reduction in PASI Score) | 28 Participants |
p-value: 0.000595% CI: [0.45, 0.89]Chi-squared
95% CI: [0.55, 0.85]
Secondary
Number of Participants Achieving PASI90 (90% or Greater Reduction in PASI Score)
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on PASI90, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). Binary measure of change in psoriasis activity; 90% or greater reduction in PASI score compared to baseline.
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ustekinumab (RCT Period) | Number of Participants Achieving PASI90 (90% or Greater Reduction in PASI Score) | 9 Participants |
| Placebo (RCT Period) | Number of Participants Achieving PASI90 (90% or Greater Reduction in PASI Score) | 0 Participants |
| Total (Active Treatment Period) | Number of Participants Achieving PASI90 (90% or Greater Reduction in PASI Score) | 19 Participants |
p-value: 0.001695% CI: [0.2, 0.62]Chi-squared
95% CI: [0.32, 0.65]
Secondary
Number of Participants Achieving Physician Global Assessment (PGA) Clear/Almost Clear
To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on PGA clear/almost clear, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). Binary measure of psoriasis disease activity at measurement time points; Physician Global Assessment score \<1.5 (clear/almost clear)
Time frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ustekinumab (RCT Period) | Number of Participants Achieving Physician Global Assessment (PGA) Clear/Almost Clear | 14 Participants |
| Placebo (RCT Period) | Number of Participants Achieving Physician Global Assessment (PGA) Clear/Almost Clear | 2 Participants |
| Total (Active Treatment Period) | Number of Participants Achieving Physician Global Assessment (PGA) Clear/Almost Clear | 18 Participants |
Comparison: Comparison during RCT period for binary Physician Global Assessmentp-value: 0.000595% CI: [0.29, 0.78]Chi-squared
95% CI: [0.3, 0.63]