Regional Variations in Alirocumab Dosing Patterns in Patients with Heterozygous Familial Hypercholesterolemia During an Open-Label Extension Study

Cardiovasc Drugs Ther. 2020 Aug;34(4):515-523. doi: 10.1007/s10557-020-06984-0.

Abstract

Purpose: During the alirocumab open-label extension study ODYSSEY OLE (open-label extension; NCT01954394), physicians could adjust alirocumab dosing for enrolled patients, who were diagnosed with heterozygous familial hypercholesterolemia (HeFH) and who had completed previous phase III clinical trials with alirocumab. This post hoc analysis evaluated the differences in physician-patient dosing decisions between the regions of Western Europe, Eastern Europe, North America, and the rest of the world (ROW).

Methods: Patients (n = 909) who received starting dose alirocumab 75 mg every 2 weeks (Q2W) during ODYSSEY OLE (patients from FH I, FH II, and LONG TERM parent studies) were included. Low-density lipoprotein cholesterol (LDL-C) levels were blinded until week 8; subsequently, LDL-C values were communicated to physicians. From week 12, dose adjustment from 75 to 150 mg Q2W, or vice versa, was possible.

Results: Mean LDL-C values used for the decision to increase dose from 75 to 150 mg Q2W were higher in Eastern Europe (3.7 mmol/L; 144.0 mg/dL) and ROW (3.8 mmol/L; 145.2 mg/dL) compared with Western Europe (3.1 mmol/L; 118.6 mg/dL) and North America (3.3 mmol/L; 126.6 mg/dL). Irrespective of region, the mean LDL-C at the time of decision to maintain at 75 mg Q2W was approximately 1.8 mmol/L (70 mg/dL). During ODYSSEY OLE (median treatment duration of 131.7 weeks), alirocumab was shown to have no unexpected long-term safety concerns.

Conclusions: In this OLE study, the observed variations in clinical treatment decisions suggest that physicians may perceive the severity of HeFH and/or the treatment of HeFH differently depending on their region.

Keywords: Alirocumab; Dose adjustment; Familial hypercholesterolemia; LDL-C; Open-label extension; PCSK9.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Anticholesteremic Agents / administration & dosage*
  • Anticholesteremic Agents / adverse effects
  • Biomarkers / blood
  • Cholesterol, LDL / blood
  • Drug Dosage Calculations
  • Drug Utilization / trends
  • Female
  • Genetic Predisposition to Disease
  • Healthcare Disparities / trends*
  • Heterozygote
  • Humans
  • Hyperlipoproteinemia Type II / blood
  • Hyperlipoproteinemia Type II / diagnosis
  • Hyperlipoproteinemia Type II / drug therapy*
  • Hyperlipoproteinemia Type II / genetics
  • Male
  • Middle Aged
  • PCSK9 Inhibitors
  • Phenotype
  • Practice Patterns, Physicians' / trends*
  • Serine Proteinase Inhibitors / administration & dosage*
  • Serine Proteinase Inhibitors / adverse effects

Substances

  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents
  • Biomarkers
  • Cholesterol, LDL
  • PCSK9 Inhibitors
  • Serine Proteinase Inhibitors
  • PCSK9 protein, human
  • alirocumab