Lomitapide for treatment of homozygous familial hypercholesterolemia: The Québec experience.
Homozygous familial hypercholesterolemia
Lomitapide
Low-density lipoprotein cholesterol
Orphan drug
Journal
Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
11
03
2020
revised:
23
07
2020
accepted:
30
07
2020
pubmed:
10
9
2020
medline:
24
6
2021
entrez:
9
9
2020
Statut:
ppublish
Résumé
Homozygous familial hypercholesterolemia (HoFH) is an orphan disease, most often caused by bi-allelic mutations of the LDLR gene. Patients with HoFH have elevated LDL-C levels >13 mmol/L, tendinous xanthomata and severe, premature atherosclerotic cardiovascular disease (ASCVD). Untreated, most HoFH patients die of ASCVD in youth. New therapeutic modalities include lomitapide, an inhibitor of microsomal triglyceride transfer protein that lowers hepatic LDL-C production. We have recently identified 79 Canadian patients with HoFH. Here, we describe our experience with lomitapide in the province of Quebec, a geographic area known to have a high prevalence of HoFH. This is a retrospective case series of 12 HoFH patients followed at three lipidology centers in the province of Quebec. Mean age of the patients was 44 ± 18 years; age at time of HoFH diagnosis ranged from 2 to 59 years. All patients were on a statin and ezetimibe 10 mg/day and five patients were treated with LDL apheresis. Treatment with lomitapide reduced LDL-C levels by 38% (intention-to-treat). Intolerable gastrointestinal side effects were observed in 3/12 patients and were the main reason for treatment discontinuation. Three patients tolerated lomitapide at doses ranging between 5 and 30 mg/day without major side effects. Downwards drug titration was necessary in the 6 remaining patients because of gastrointestinal side effects (n = 5) and elevated liver enzymes (n = 1), and 2 of them finally discontinued treatment. Lomitapide may be used to further decrease LDL-C in HoFH patients; gastrointestinal side effects and hepatic toxicity may limit adherence.
Sections du résumé
BACKGROUND AND AIMS
Homozygous familial hypercholesterolemia (HoFH) is an orphan disease, most often caused by bi-allelic mutations of the LDLR gene. Patients with HoFH have elevated LDL-C levels >13 mmol/L, tendinous xanthomata and severe, premature atherosclerotic cardiovascular disease (ASCVD). Untreated, most HoFH patients die of ASCVD in youth. New therapeutic modalities include lomitapide, an inhibitor of microsomal triglyceride transfer protein that lowers hepatic LDL-C production. We have recently identified 79 Canadian patients with HoFH. Here, we describe our experience with lomitapide in the province of Quebec, a geographic area known to have a high prevalence of HoFH.
METHODS
This is a retrospective case series of 12 HoFH patients followed at three lipidology centers in the province of Quebec.
RESULTS
Mean age of the patients was 44 ± 18 years; age at time of HoFH diagnosis ranged from 2 to 59 years. All patients were on a statin and ezetimibe 10 mg/day and five patients were treated with LDL apheresis. Treatment with lomitapide reduced LDL-C levels by 38% (intention-to-treat). Intolerable gastrointestinal side effects were observed in 3/12 patients and were the main reason for treatment discontinuation. Three patients tolerated lomitapide at doses ranging between 5 and 30 mg/day without major side effects. Downwards drug titration was necessary in the 6 remaining patients because of gastrointestinal side effects (n = 5) and elevated liver enzymes (n = 1), and 2 of them finally discontinued treatment.
CONCLUSIONS
Lomitapide may be used to further decrease LDL-C in HoFH patients; gastrointestinal side effects and hepatic toxicity may limit adherence.
Identifiants
pubmed: 32906018
pii: S0021-9150(20)30410-X
doi: 10.1016/j.atherosclerosis.2020.07.028
pii:
doi:
Substances chimiques
Anticholesteremic Agents
0
BMS201038
0
Benzimidazoles
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
54-63Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.