Ixekizumab treatment shows a neutral impact on cardiovascular parameters in patients with moderate-to-severe plaque psoriasis: Results from UNCOVER-1, UNCOVER-2, and UNCOVER-3

J Am Acad Dermatol. 2018 Jul;79(1):104-109.e8. doi: 10.1016/j.jaad.2018.02.074. Epub 2018 Mar 13.

Abstract

Background: The impact of ixekizumab treatment for psoriasis on cardiovascular-related parameters in patients is unknown.

Objective: To investigate cardiovascular-related parameters in patients with psoriasis treated with ixekizumab.

Methods: In phase 3 trials, patients with moderate-to-severe psoriasis were randomized and treated with placebo, ixekizumab, or etanercept during the induction period (weeks 0-12; UNCOVER-1, UNCOVER-2, and UNCOVER-3). At week 12, responders were rerandomized to receive placebo or ixekizumab through the maintenance period (weeks 12-60; UNCOVER-1 and UNCOVER-2). Laboratory measures (fasting lipid profiles, glucose level, or high-sensitivity C-reactive protein [hsCRP] level), weight, blood pressure, and electrocardiograms were obtained through 60 weeks.

Results: Baseline parameters were within normal ranges with the exception of elevated triglyceride and hsCRP levels. After maintenance dosing, no significant changes were observed versus placebo for total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, triglyceride, apolipoprotein A1, apolipoprotein B, or fasting glucose levels or for systolic/diastolic blood pressure at 60 weeks. Importantly, low-density lipoprotein-to-high-density lipoprotein ratios remained stable during the induction and maintenance periods. HsCRP concentrations were significantly reduced versus placebo at 12 weeks and remained reduced at 60 weeks, although not significantly. Although transient changes were observed for some parameters during the induction period, these changes did not persist into the maintenance period.

Limitations: A lack of echocardiogram evaluations.

Conclusions: Ixekizumab had a neutral impact on cardiovascular-related parameters in patients with psoriasis.

Keywords: IL-17A; UNCOVER; cardiovascular; cholesterol; hsCRP; ixekizumab; psoriasis.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • C-Reactive Protein / drug effects
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / physiopathology
  • Cholesterol / blood
  • Dermatologic Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Psoriasis / diagnosis*
  • Psoriasis / drug therapy*
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Dermatologic Agents
  • C-Reactive Protein
  • Cholesterol
  • ixekizumab