Vascular Inflammation in Psoriasis-Ustekinumab (VIP-U)

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT02187172
• Collaborator: Janssen Scientific Affairs, LLC (Industry)
• Enrollment: 43
• Location: 1
• Arms: 2
• Duration (Months): 50.4
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis; Cardiovascular Disease	Drug: Ustekinumab; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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).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).
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A PHASE IV, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE EFFECTS OF USTEKINUMAB ON VASCULAR INFLAMMATION IN PSORIASIS
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Sep 11, 2018
• Actual Study Completion Date: Sep 11, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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. Patient will receive total of 52 weeks of ustekinumab (12 weeks during RCT phase, 40 weeks post RCT phase). The end of study is at Week 52 for this arm.	Drug: Ustekinumab
Placebo Comparator: Placebo Placebo subcutaneous injection will be given according to the same dose and schedule as the active comparator until week 12 (end of RCT phase). At week 12, ustekinumab will be administered according according to the same injection schedule as the active comparator arm for 52 weeks. Patient will receive total of 52 weeks of ustekinumab (0 weeks during RCT phase, 52 weeks post RCT phase). The end of study is at Week 64 for this arm.	Drug: Ustekinumab; Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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).

3. 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).

4. 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).

5. 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).

6. 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).

7. 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).

8. 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).

9. 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).

10. 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).

11. 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).

12. 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).

13. 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).

14. 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).

15. 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).

16. 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).

17. 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).

18. 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).

19. 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).

20. 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).

21. 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).

22. 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).

23. 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).

24. 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).

25. 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).

26. 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).

27. 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).

28. 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).

29. 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).

30. 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).

31. 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).

32. 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).

33. 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).

34. 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).

35. 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).

36. 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).

37. 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).

38. 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).

39. 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).

40. 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).

41. 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)].

42. 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).

43. 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).

44. 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).

45. 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).

46. 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).

47. 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).

48. 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).

Secondary Outcome Measures

1. 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.

2. 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.

3. 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)

4. 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).

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

1. as determined by subject interview of his/her medical history.

1. Moderate to severe psoriasis defined by ≥ 10 percent Body Surface Area (BSA) involvement at the Baseline (Week 0) visit.

2. PASI score of ≥ 12 at the Baseline (Week 0) visit.

3. Subject is a candidate for systemic therapy and has active psoriasis despite prior treatment with topical agents.

4. Women are eligible to participate in the study if they meet one of the following criteria:

5. 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.

6. Women who are postmenopausal (for at least one year), sterile, or hysterectomized are eligible to participate.

7. Women who have undergone tubal ligation are eligible to participate.

8. Women who agree to be sexually abstinent, defined as total abstinence from sexual intercourse, as a form of contraception, are eligible to participate.

9. Men are eligible to participate in the study if they meet one of the following criteria:

10. 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.

11. 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.

12. Have a female partner who is postmenopausal (for at least one year), sterile, or hysterectomized;

13. Have a female partner who has undergone tubal ligation,

14. Agree to be sexually abstinent, defined as total abstinence from sexual intercourse, as a form of contraception.

15. 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.

16. 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.

1. Subject is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.

2. 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.

3. 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%.

4. Uncontrolled hypertension, with measured systolic blood pressure >180 mmHg or diastolic blood pressure >90 mmHg

5. 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.

1. 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.

2. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study.

3. Male subject who is considering fathering a child during the study.

4. 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)

1. Recent history of substance abuse or psychiatric illness that could preclude compliance with the protocol.

2. History of any substance abuse within 365 days of screening visit

3. Alcohol use >14 drinks per week at the screening visit or within 30 days of the screening period

4. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• Janssen Scientific Affairs, LLC

Investigators

• Principal Investigator: Joel M Gelfand, MD, MSCE, University of Pennsylvania

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 25, 2019

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT02187172
• Other Study ID Numbers: 820124
• First Posted: Jul 10, 2014
• Last Update Posted: Aug 15, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by University of Pennsylvania: Psoriasis; Cardiovascular Disease; Vascular Inflammation; Lipid Biomarkers; FDG-PET/CT
• Additional relevant MeSH terms: Cardiovascular Diseases; Psoriasis; Inflammation; Ustekinumab

Study Results

Participant Flow

Arm/Group Title	Ustekinumab	Placebo
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12 (randomized controlled trial (RCT) phase). Continue to receive ustekinumab for additional 40 weeks for a total of 52 weeks of ustekinumab. The end of study is at Week 52 for this arm.	Randomized to receive Placebo from day 0 until week 12 (RCT phase). Receive ustekinumab from week 12 until week 64 for a total of 52 weeks of ustekinumab. The end of study is at Week 64 for this arm.
Period Title: Overall Study
STARTED	22	21
RCT Phase Completed	22	19
COMPLETED	19	15
NOT COMPLETED	3	6

Baseline Characteristics

Arm/Group Title	Ustekinumab (Stelara)	Placebo	Total
Arm/Group Description	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	Placebo subcutaneous injection will be given according to the same dose and schedule as the active comparator. Ustekinumab Placebo	Total of all reporting groups
Overall Participants	22	21	43
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.45 (13.6)	45.33 (12.76)	42.33 (13.38)
Sex: Female, Male (Count of Participants)
Female	6 27.3%	7 33.3%	13 30.2%
Male	16 72.7%	14 66.7%	30 69.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 9.1%	2 9.5%	4 9.3%
Not Hispanic or Latino	19 86.4%	19 90.5%	38 88.4%
Unknown or Not Reported	1 4.5%	0 0%	1 2.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 4.5%	2 9.5%	3 7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 9.1%	5 23.8%	7 16.3%
White	19 86.4%	12 57.1%	31 72.1%
More than one race	0 0%	2 9.5%	2 4.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	33.24 (7.95)	33.32 (6.29)	33.28 (7.1)
Medical History (participants) [Number]
Arthritis	0 0%	1 4.8%	1 2.3%
Coronary Artery Disease	1 4.5%	1 4.8%	2 4.7%
Depression	2 9.1%	2 9.5%	4 9.3%
Diabetes	0 0%	1 4.8%	1 2.3%
Hyperlipidemia	5 22.7%	2 9.5%	7 16.3%
Stroke	1 4.5%	0 0%	1 2.3%
Statin Use	3 13.6%	3 14.3%	6 14%
Body Surface Area (BSA) (percentage of total body surface area) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of total body surface area]	26.18 (17.51)	23.71 (15.58)	24.98 (16.45)
Psoriasis Area Severity Index (PASI) score (composite score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [composite score]	20.03 (7.47)	19.82 (7.64)	19.93 (7.46)
Physician Global Assessment (PGA) (calculated score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [calculated score]	3.5 (0.57)	3.38 (0.8)	3.44 (0.69)
Psoriasis duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	16.45 (11.02)	20.29 (14.41)	18.13 (12.58)
Psoriasis treatment history (participants) [Number]
Biologics	10 45.5%	9 42.9%	19 44.2%
Systemics	6 27.3%	2 9.5%	8 18.6%
Phototherapy	10 45.5%	9 42.9%	19 44.2%
Psoriatic Arthritis (PsA) present (Count of Participants)
Count of Participants [Participants]	1 4.5%	6 28.6%	7 16.3%
Age at PsA diagnosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22 (0)	43.6 (14.33)	40 (15.56)

Outcome Measures

1. Primary Outcome

Title	Change in Vascular Inflammation
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	22	19	38
Mean (Standard Error) [TBR max]	-0.1015 (0.0465)	0.1442 (0.0137)	-0.0151 (0.0353)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2456
	Confidence Interval	(2-Sided) 95%; -0.3873 to -0.1040
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0700
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6718
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.0151
	Confidence Interval	(2-Sided) 95%; -0.0867 to 0.0565
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0353
	Estimation Comments

2. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: Intercellular Adhesion Molecule-1 (ICAM-1)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [ng/mL]	10.83 (26.30)	75.80 (37.19)	6.65 (22.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1159
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-64.97
	Confidence Interval	(2-Sided) 95%; -115.83 to 25.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 44.88
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7666
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.65
	Confidence Interval	(2-Sided) 95%; -38.41 to 51.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 22.24
	Estimation Comments

3. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: Vascular Cell Adhesion Molecule-1 (VCAM-1)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [ng/mL]	-20.36 (18.39)	60.53 (24.76)	-1.99 (14.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0115
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-80.89
	Confidence Interval	(2-Sided) 95%; -142.55 to -19.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 30.46
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8883
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.99
	Confidence Interval	(2-Sided) 95%; -30.58 to 26.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 14.11
	Estimation Comments

4. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: C-reactive Protein (CRP)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [ng/mL]	-2886.57 (2851.16)	140.64 (1108.54)	-1974.63 (1659.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3472
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3027.21
	Confidence Interval	(2-Sided) 95%; -9465.95 to 3411.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3180.58
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Combined ustekinumab and placebo groups for active treatment period analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2416
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1974.63
	Confidence Interval	(2-Sided) 95%; -5336.30 to 1387.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1659.11
	Estimation Comments

5. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: Ferritin
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [ng/mL]	-12.32 (39.16)	-32.97 (27.40)	47.00 (35.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6742
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	20.66
	Confidence Interval	(2-Sided) 95%; -78.03 to 119.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 24.75
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1979
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	47.00
	Confidence Interval	(2-Sided) 95%; -25.63 to 11963
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 35.84
	Estimation Comments

6. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: Serum Amyloid A (SAA)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [ng/mL]	-7687.80 (7389.00)	196.49 (203.34)	-3782.54 (4073.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3173
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7884.29
	Confidence Interval	(2-Sided) 95%; -23634.67 to 7566.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7780.29
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3591
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3782.54
	Confidence Interval	(2-Sided) 95%; -12035.72 to 4470.64
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4073.25
	Estimation Comments

7. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: Interferon-gamma (INF-g)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [pg/mL]	-0.03 (2.25)	0.04 (0.95)	-1.09 (1.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9767
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -5.22 to 5.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.54
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3205
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.09
	Confidence Interval	(2-Sided) 95%; -3.29 to 1.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.09
	Estimation Comments

8. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: Monocyte Chemoattractant Protein-1 (MCP-1)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [pg/mL]	-14.66 (15.51)	0.13 (12.09)	-7.24 (11.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4632
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-14.79
	Confidence Interval	(2-Sided) 95%; -55.19 to 25.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.96
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5316
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.24
	Confidence Interval	(2-Sided) 95%; -30.47 to 15.99
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.47
	Estimation Comments

9. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: Tumor Necrosis Factor-alpha (TNF-a)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [pg/mL]	-0.22 (0.51)	0.68 (0.44)	-0.67 (0.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1928
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.90
	Confidence Interval	(2-Sided) 95%; -2.27 to 0.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.68
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0580
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -1.36 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

10. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: GlycA
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [umol/L]	-0.70 (7.42)	3.44 (8.76)	-8.35 (8.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7185
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.14
	Confidence Interval	(2-Sided) 95%; -27.24 to 18.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.41
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3271
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.35
	Confidence Interval	(2-Sided) 95%; -25.40 to 8.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.41
	Estimation Comments

11. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: Interleukin (IL)-1b
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [pg/mL]	0.07 (0.38)	0.60 (0.34)	-0.31 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3124
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -1.56 to 0.51
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.51
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0106
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -0.54 to -0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

12. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: IL-2ra
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [ng/mL]	-79.07 (28.51)	-8.31 (15.48)	71.72 (132.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0408
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-70.76
	Confidence Interval	(2-Sided) 95%; -138.42 to -3.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 33.42
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5926
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	71.72
	Confidence Interval	(2-Sided) 95%; -197.50 to 340.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 132.87
	Estimation Comments

13. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: IL-12/23
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [pg/mL]	196.84 (43.59)	5.35 (4.63)	171.21 (20.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	191.49
	Confidence Interval	(2-Sided) 95%; 98.18 to 284.81
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 46.10
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	171.21
	Confidence Interval	(2-Sided) 95%; 130.08 to 212.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 20.30
	Estimation Comments

14. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: IL-17a
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [pg/mL]	-1.46 (0.39)	1.17 (0.94)	-1.15 (0.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0110
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.63
	Confidence Interval	(2-Sided) 95%; -4.62 to -0.64
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.98
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.15
	Confidence Interval	(2-Sided) 95%; -1.79 to -0.51
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments

15. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: IL-18
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [pg/mL]	301.21 (483.77)	456.52 (487.49)	-407.43 (180.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8227
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-155.31
	Confidence Interval	(2-Sided) 95%; -1548.66 to 1238.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 688.28
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0302
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-407.43
	Confidence Interval	(2-Sided) 95%; -773.57 to -41.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 180.70
	Estimation Comments

16. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: IL-6
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [pg/mL]	-0.45 (0.22)	0.02 (0.33)	-0.38 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2333
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.47
	Confidence Interval	(2-Sided) 95%; -1.25 to 0.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: -0.47
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0713
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -0.80 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.21
	Estimation Comments

17. Primary Outcome

Title	Change in Inflammatory Biomarker Levels: IL-8
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [pg/mL]	2.46 (3.35)	19.33 (16.02)	-2.23 (1.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2869
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-16.87
	Confidence Interval	(2-Sided) 95%; -48.48 to 14.75
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 15.62
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1988
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.23
	Confidence Interval	(2-Sided) 95%; -5.69 to 1.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.71
	Estimation Comments

18. Primary Outcome

Title	Change in Lipid Biomarker Levels: Triglycerides
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [mg/dL]	0.48 (9.42)	-1.58 (8.70)	10.55 (8.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8744
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.06
	Confidence Interval	(2-Sided) 95%; -24.09 to 28.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 12.91
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2093
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	10.55
	Confidence Interval	(2-Sided) 95%; -6.18 to 27.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.26
	Estimation Comments

19. Primary Outcome

Title	Change in Lipid Biomarker Levels: Total Cholesterol
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [mg/dL]	12.57 (5.04)	-6.63 (5.45)	-0.79 (4.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0135
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	19.20
	Confidence Interval	(2-Sided) 95%; 4.21 to 34.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.41
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8499
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.79
	Confidence Interval	(2-Sided) 95%; -9.19 to 7.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.14
	Estimation Comments

20. Primary Outcome

Title	Change in Lipid Biomarker Levels: High-density Lipoprotein (HDL) Cholesterol
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [mg/dL]	2.24 (1.31)	-1.42 (1.46)	1.92 (1.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0693
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.66
	Confidence Interval	(2-Sided) 95%; -0.30 to 7.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.96
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1841
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.92
	Confidence Interval	(2-Sided) 95%; -0.96 to 4.80
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.42
	Estimation Comments

21. Primary Outcome

Title	Change in Lipid Biomarker Levels: HDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	-0.02 (0.69)	-1.27 (0.77)	0.91 (0.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2305
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; -0.83 to 3.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.03
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2189
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; -0.53 to 2.37
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.72
	Estimation Comments

22. Primary Outcome

Title	Change in Lipid Biomarker Levels: HDL Particle Size
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nm]	0.08 (0.05)	0.19 (0.10)	0.17 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3212
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.34 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0137
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; 0.04 to 0.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

23. Primary Outcome

Title	Change in Lipid Biomarker Levels: Large-HDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	0.46 (0.38)	0.33 (0.47)	0.51 (0.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8383
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -1.09 to 1.33
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.60
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1651
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; -0.22 to 1.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.36
	Estimation Comments

24. Primary Outcome

Title	Change in Lipid Biomarker Levels: Small-HDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	-0.02 (1.15)	-2.52 (1.25)	0.21 (0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1502
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.49
	Confidence Interval	(2-Sided) 95%; -0.94 to 5.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.70
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8054
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; -1.49 to 1.91
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.84
	Estimation Comments

25. Primary Outcome

Title	Change in Lipid Biomarker Levels: Medium-HDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	-0.56 (1.21)	0.81 (1.17)	0.17 (0.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4235
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.37
	Confidence Interval	(2-Sided) 95%; -4.79 to 2.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.69
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8653
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; -1.80 to 2.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.97
	Estimation Comments

26. Primary Outcome

Title	Change in Lipid Biomarker Levels: Large Medium-HDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	0.02 (1.26)	1.14 (1.43)	0.77 (1.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5580
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.12
	Confidence Interval	(2-Sided) 95%; -4.95 to 2.71
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.89
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4454
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; -1.25 to 2.80
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.00
	Estimation Comments

27. Primary Outcome

Title	Change in Lipid Biomarker Levels: Low-density Lipoprotein (LDL) Cholesterol
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [mg/dL]	12.52 (4.21)	-8.84 (5.25)	-2.92 (4.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0027
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	21.37
	Confidence Interval	(2-Sided) 95%; 7.86 to 34.87
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.67
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4775
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.92
	Confidence Interval	(2-Sided) 95%; -11.17 to 5.33
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.07
	Estimation Comments

28. Primary Outcome

Title	Change in Lipid Biomarker Levels: LDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	112.67 (46.44)	-118.11 (52.45)	-31.89 (41.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	230.77
	Confidence Interval	(2-Sided) 95%; 89.47 to 372.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 69.80
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4493
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-31.89
	Confidence Interval	(2-Sided) 95%; -116.40 to 52.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 41.71
	Estimation Comments

29. Primary Outcome

Title	Change in Lipid Biomarker Levels: LDL Particle Size
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	0.20 (0.11)	0.15 (0.13)	0.03 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8008
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.17
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8068
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

30. Primary Outcome

Title	Change in Lipid Biomarker Levels: Small-LDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	24.36 (38.72)	-22.61 (40.61)	4.68 (33.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4079
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	46.96
	Confidence Interval	(2-Sided) 95%; -66.65 to 160.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 56.12
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8907
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.68
	Confidence Interval	(2-Sided) 95%; -63.91 to 73.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 33.85
	Estimation Comments

31. Primary Outcome

Title	Change in Lipid Biomarker Levels: Large-LDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	28.95 (26.87)	21.95 (41.87)	-24.76 (32.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8866
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.01
	Confidence Interval	(2-Sided) 95%; -91.80 to 105.81
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 48.81
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4527
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-24.74
	Confidence Interval	(2-Sided) 95%; -90.78 to 41.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 32.59
	Estimation Comments

32. Primary Outcome

Title	Change in Lipid Biomarker Levels: Very Large-LDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	93.95 (45.38)	-100.74 (48.29)	-29.16 (38.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0056
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	194.69
	Confidence Interval	(2-Sided) 95%; 60.61 to 328.77
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 66.23
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4478
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-29.16
	Confidence Interval	(2-Sided) 95%; -106.17 to 47.85
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 38.01
	Estimation Comments

33. Primary Outcome

Title	Change in Lipid Biomarker Levels: Very Low-density Lipoprotein (VLDL) Particle Size
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	3.19 (2.19)	0.04 (1.69)	1.50 (1.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2704
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.14
	Confidence Interval	(2-Sided) 95%; -2.55 to 8.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.81
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2950
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.50
	Confidence Interval	(2-Sided) 95%; -1.36 to 4.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.41
	Estimation Comments

34. Primary Outcome

Title	Change in Lipid Biomarker Levels: VLDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	-9.32 (4.85)	7.42 (4.34)	-0.11 (3.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0149
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-16.74
	Confidence Interval	(2-Sided) 95%; -30.03 to -3.45
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.57
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9734
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -6.93 to 6.71
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.37
	Estimation Comments

35. Primary Outcome

Title	Change in Lipid Biomarker Levels: VLDL Triglycerides
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [mg/dL]	-4.88 (8.85)	4.33 (7.57)	11.14 (7.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4384
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-9.21
	Confidence Interval	(2-Sided) 95%; -33.03 to 14.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.76
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1373
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.14
	Confidence Interval	(2-Sided) 95%; -3.72 to 25.99
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.33
	Estimation Comments

36. Primary Outcome

Title	Change in Lipid Biomarker Levels: Small-VLDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	-5.84 (2.72)	9.87 (5.27)	-0.50 (2.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0097
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-15.71
	Confidence Interval	(2-Sided) 95%; -27.39 to -4.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.77
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8119
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -4.69 to 3.70
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.07
	Estimation Comments

37. Primary Outcome

Title	Change in Lipid Biomarker Levels: Medium-VLDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	-3.50 (2.98)	-3.84 (3.50)	-1.86 (2.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9415
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; -8.91 to 9.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.57
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4485
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.86
	Confidence Interval	(2-Sided) 95%; -6.77 to 3.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.43
	Estimation Comments

38. Primary Outcome

Title	Change in Lipid Biomarker Levels: Large Medium-VLDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	-2.89 (3.33)	-2.97 (3.98)	0.38 (2.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9880
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -10.37 to 10.53
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.16
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8836
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; -4.86 to 5.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.59
	Estimation Comments

39. Primary Outcome

Title	Change in Lipid Biomarker Levels: Large-VLDL Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	0.29 (0.86)	0.57 (0.99)	2.30 (1.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8321
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -2.91 to 2.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.30
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0394
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.30
	Confidence Interval	(2-Sided) 95%; 0.12 to 4.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.08
	Estimation Comments

40. Primary Outcome

Title	Change in Lipid Biomarker Levels: Intermediate-density Lipoprotein (IDL) Particle Number
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [nmol/L]	50.86 (25.89)	-101.79 (36.04)	-2.97 (25.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	152.68
	Confidence Interval	(2-Sided) 95%; 64.07 to 241.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 43.76
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9085
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.97
	Confidence Interval	(2-Sided) 95%; -55.04 to 49.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 25.70
	Estimation Comments

41. Primary Outcome

Title	Change in Lipid Biomarker Levels: Cholesterol Efflux Capacity
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [unitless (see description)]	0.09 (0.03)	0.03 (0.03)	0.04 (0.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1792
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.04
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2559
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

42. Primary Outcome

Title	Change in Lipid Biomarker Levels: Apolipoprotein-B
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [ug/mL]	0.11 (0.09)	-0.04 (0.09)	0.10 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2453
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.15
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1087
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.06
	Estimation Comments

43. Primary Outcome

Title	Change in Lipid Biomarker Levels: Fetuin-A
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [ug/mL]	10.22 (29.47)	-38.21 (56.05)	-49.56 (27.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4368
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	48.43
	Confidence Interval	(2-Sided) 95%; -76.31 to 173.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 61.62
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0833
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-49.56
	Confidence Interval	(2-Sided) 95%; -105.97 to 6.85
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 27.84
	Estimation Comments

44. Primary Outcome

Title	Change in Metabolic Biomarker Levels: Adiponectin
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [ug/mL]	0.04 (0.79)	0.32 (0.77)	0.38 (0.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8036
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -2.52 to 1.97
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.11
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4608
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; -0.65 to 1.40
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.51
	Estimation Comments

45. Primary Outcome

Title	Change in Metabolic Biomarker Levels: Leptin
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [pg/mL]	8022.19 (2576.52)	4701.61 (2184.57)	6926.25 (2257.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3370
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3320.58
	Confidence Interval	(2-Sided) 95%; -3592.52 to 10233.67
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3414.90
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0040
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6926.25
	Confidence Interval	(2-Sided) 95%; 2351.43 to 11501.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2257.84
	Estimation Comments

46. Primary Outcome

Title	Change in Metabolic Biomarker Levels: Insulin
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [pg/mL]	36.19 (116.40)	105.13 (51.42)	-7.96 (85.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6042
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-68.95
	Confidence Interval	(2-Sided) 95%; -335.97 to 198.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 131.90
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9267
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.96
	Confidence Interval	(2-Sided) 95%; -182.18 to 166.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 85.98
	Estimation Comments

47. Primary Outcome

Title	Change in Metabolic Biomarker Levels: Glucose
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	22	19	39
Mean (Standard Error) [mg/dL]	2.41 (3.34)	-1.79 (4.02)	3.41 (3.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4226
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.20
	Confidence Interval	(2-Sided) 95%; -6.28 to 14.68
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.18
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3270
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.41
	Confidence Interval	(2-Sided) 95%; -3.54 to 10.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.43
	Estimation Comments

48. Primary Outcome

Title	Change in Metabolic Biomarker Levels: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	19	38
Mean (Standard Error) [unitless (see description)]	0.07 (1.37)	0.55 (0.49)	-0.07 (0.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7507
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -3.56 to 2.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.52
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments	Global change from baseline after 52 weeks of active treatment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9348
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -1.88 to 1.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.89
	Estimation Comments

49. Secondary Outcome

Title	Number of Participants Achieving PASI75 (75% or Greater Reduction in PASI Score)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	22	19	39
Count of Participants [Participants]	17 77.3%	2 9.5%	28 65.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference of proportions
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.45 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments
	Type of Statistical Test	Other
	Comments	95% CI of proportion achieving PASI75 at end of study
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.55 to 0.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

50. Secondary Outcome

Title	Number of Participants Achieving PASI90 (90% or Greater Reduction in PASI Score)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	22	19	39
Count of Participants [Participants]	9 40.9%	0 0%	19 44.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference of proportions
	Estimated Value	0.41
	Confidence Interval	(2-Sided) 95%; 0.20 to 0.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments
	Type of Statistical Test	Other
	Comments	95% CI of proportion achieving PASI90 at end of study
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95%; 0.32 to 0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

51. Secondary Outcome

Title	Number of Participants Achieving Physician Global Assessment (PGA) Clear/Almost Clear
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	22	19	39
Count of Participants [Participants]	14 63.6%	2 9.5%	18 41.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments	Comparison during RCT period for binary Physician Global Assessment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference of proportions
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95%; 0.29 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments
	Type of Statistical Test	Other
	Comments	95% CI of proportion achieving PGA clear/almost clear at end of study
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; 0.30 to 0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

52. Secondary Outcome

Title	Change in Patient-Reported Outcomes: MEDFICTS
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	22	19	41
Mean (Standard Error) [MEDFICTS score]	-5.68 (3.97)	-14.00 (4.98)	8.32 (6.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1944
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8.32
	Confidence Interval	(2-Sided) 95%; -4.42 to 21.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.30
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.33
	Confidence Interval	(2-Sided) 95%; -19.40 to -5.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.50
	Estimation Comments

53. Secondary Outcome

Title	Change in Patient-reported Physical Activity Assessments: IPAQ
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ustekinumab (RCT Period)	Placebo (RCT Period)	Total (Active Treatment Period)
Arm/Group Description	Randomized to receive Ustekinumab (Stelara) from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Randomized to receive Placebo from day 0 until week 12. Outcome measures reflect changes at week 12 compared to baseline.	Combined ustekinumab and placebo groups for active treatment period analysis. Outcome measures reflect changes at end of study (week 52 for group randomized to Ustekinumab, week 64 for group randomized to Placebo) compared to baseline.
Measure Participants	21	16	37
Mean (Standard Error) [MET-minutes/week]	73.69 (808.45)	853.28 (562.37)	-779.59 (1049.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ustekinumab (RCT Period), Placebo (RCT Period)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4628
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-779.59
	Confidence Interval	(2-Sided) 95%; -2911.19 to 1352.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1049.99
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Total (Active Treatment Period)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2209
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-910.84
	Confidence Interval	(2-Sided) 95%; -2395.95 to 574.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 729.96
	Estimation Comments

Adverse Events

Time Frame	52 weeks for Ustekinumab arm, 64 weeks for Placebo arm.
Adverse Event Reporting Description	For each subject, AEs and SAEs occurring after informed consent is obtained should be recorded until the subject has completed his/her participation in the study. A serious adverse event must be reported if it occurs during a subject's participation in the Study (whether receiving Study Product or not) and within 12 weeks of receiving the last dose of Study Product in a clinical trial, whichever is longer.
Arm/Group Title	Ustekinumab (Stelara)		Placebo (RCT Period)		Placebo (Active Treatment Period)
Arm/Group Description	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. From Baseline to Week 52.		Placebo subcutaneous injection will be given according to the same dose and schedule as the active comparator. From Baseline to Week 12 (RCT period only).		Placebo arm after crossing over to receive ustekinumab, following the same dosing schedule of the Ustekinumab arm. From Week 12 to Week 64 (52 weeks of active treatment period).
All Cause Mortality
	Ustekinumab (Stelara)		Placebo (RCT Period)		Placebo (Active Treatment Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/21 (0%)		0/19 (0%)
Serious Adverse Events
	Ustekinumab (Stelara)		Placebo (RCT Period)		Placebo (Active Treatment Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/21 (0%)		3/19 (15.8%)
Cardiac disorders
Hypotension	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Reproductive system and breast disorders
Endometritis	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Vascular disorders
Stroke	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Vasovagal reaction	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Other (Not Including Serious) Adverse Events
	Ustekinumab (Stelara)		Placebo (RCT Period)		Placebo (Active Treatment Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/22 (63.6%)		3/21 (14.3%)		16/19 (84.2%)
Ear and labyrinth disorders
External ear pain	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Ear And Labyrinth Disorders/Ear Pain	0/22 (0%)	0	0/21 (0%)	0	2/19 (10.5%)	2
Gastrointestinal disorders
Gastritis	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Stomach pain	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
General disorders
Toothache	1/22 (4.5%)	1	0/21 (0%)	0	1/19 (5.3%)	1
Hepatobiliary disorders
Alkaline Phosphatase Increased	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Hepatic Lesion	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Immune system disorders
Allergies to foods, food additives, drugs and other chemicals	0/22 (0%)	0	0/21 (0%)	0	2/19 (10.5%)	2
Infections and infestations
Common cold	6/22 (27.3%)	6	0/21 (0%)	0	2/19 (10.5%)	2
Upper respiratory infection	11/22 (50%)	11	3/21 (14.3%)	3	4/19 (21.1%)	4
Urinary tract infection	2/22 (9.1%)	2	0/21 (0%)	0	0/19 (0%)	0
Latent Tuberculosis	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Pyelonephritis	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Trichomoniasis	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Viral Infection	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/22 (9.1%)	2	0/21 (0%)	0	0/19 (0%)	0
Fracture	2/22 (9.1%)	2	0/21 (0%)	0	0/19 (0%)	0
Pain/Pain in extremity	1/22 (4.5%)	2	0/21 (0%)	0	0/19 (0%)	0
Pain	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Nervous system disorders
Dizziness	2/22 (9.1%)	2	0/21 (0%)	0	0/19 (0%)	0
Psychiatric disorders
Anxiety	2/22 (9.1%)	2	0/21 (0%)	0	0/19 (0%)	0
Anhedonia	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Panic Attack	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Reproductive system and breast disorders
Uterine hemorrhage	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Uterine Fibroids Enlarged	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Productive cough	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	2/22 (9.1%)	2	0/21 (0%)	0	1/19 (5.3%)	1
Blistering	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Dermatitis Irritant Contact	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Dysplastic Nevus	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Rash/Rash Acneiform/Maculo-Papular	1/22 (4.5%)	1	0/21 (0%)	0	3/19 (15.8%)	3
Would Healing Delayed	0/22 (0%)	0	0/21 (0%)	0	1/19 (5.3%)	1
Vascular disorders
Hypertension	1/22 (4.5%)	1	0/21 (0%)	0	1/19 (5.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.