A Randomized Placebo-Controlled Trial of Secukinumab on Aortic Vascular Inflammation in Moderate-to-Severe Plaque Psoriasis (VIP-S)

J Invest Dermatol. 2020 Sep;140(9):1784-1793.e2. doi: 10.1016/j.jid.2020.01.025. Epub 2020 Feb 21.

Abstract

Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has reported high efficacy with a favorable safety profile in various psoriatic disease manifestations. Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, patients with moderate-to-severe psoriasis received secukinumab for 40 weeks. Vascular inflammation using 18F-2-fluorodeoxyglucose-positron emission tomography/computed tomography imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. The difference in change in aortic inflammation from baseline to week 12 for secukinumab (n = 46) versus placebo (n = 45) was -0.053 (95% confidence interval = -0.169 to 0.064; P= 0.37). Small increases in total cholesterol, low-density lipoprotein, and low-density lipoprotein particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At week 52, reductions in TNF-α (P= 0.0063) and ferritin (P= 0.0354), and an increase in fetuin-A (P= 0.0024), were observed with secukinumab treatment compared with baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared with baseline. Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.

Trial registration: ClinicalTrials.gov NCT02690701.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Aorta / diagnostic imaging
  • Aorta / drug effects
  • Aorta / immunology
  • Arteritis / blood
  • Arteritis / diagnosis
  • Arteritis / drug therapy*
  • Arteritis / immunology
  • Biomarkers / blood
  • Double-Blind Method
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / immunology
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / diagnosis*
  • Metabolic Syndrome / immunology
  • Metabolic Syndrome / prevention & control
  • Middle Aged
  • Placebos / administration & dosage
  • Placebos / adverse effects
  • Positron Emission Tomography Computed Tomography
  • Psoriasis / blood
  • Psoriasis / complications
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • IL17A protein, human
  • Interleukin-17
  • Placebos
  • Fluorodeoxyglucose F18
  • secukinumab

Associated data

  • ClinicalTrials.gov/NCT02690701