Management of homozygous familial hypercholesterolaemia in two brothers

Real, José T.; Arbona, Cristina; Goterris, Rosa; Ascaso, Juan F.

doi:10.1136/bcr-2017-222155

Cited by 7 publications

(4 citation statements)

References 17 publications

(33 reference statements)

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“…This paediatric case series—the first of its kind for lomitapide in HoFH—demonstrates that lomitapide has been effective in reducing LDL-C in paediatric patients with HoFH, and suggests that the drug has a similar adverse event and usage profile to that observed in adult patients. Consistent with real-world data from adult patients [15, 28], this paediatric case series shows a greater reduction in LDL-C at a lower mean dose of lomitapide than in the phase 3 study. This is a curious finding but is replicated across data sets and may be explained by the titration of the dose of lomitapide to desired LDL-C reduction as opposed to the ‘forced’ escalation protocol based on tolerability as used in the phase 3 study.…”

Section: Discussionsupporting

confidence: 86%

Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia

et al. 2019

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IntroductionHomozygous familial hypercholesterolaemia (HoFH) is a rare, autosomal disease affecting the clearance of low-density lipoprotein cholesterol (LDL-C) from circulation, and leading to early-onset atherosclerotic cardiovascular disease (ASCVD). Treatment consists mainly of statins, lipoprotein apheresis (LA) and, more recently, the microsomal triglyceride transfer protein inhibitor lomitapide. Lomitapide is not licensed for use in children, but has been made available through an expanded access programme or on a named patient basis.MethodsThis case series includes 11 HoFH patients in 10 different centres in eight countries, less than 18 years of age (mean 11.6 ± 1.1 years, 64% male), with signs of ASCVD, and who have received treatment with lomitapide (mean dose 24.5 ± 4.3 mg/day; mean exposure 20.0 ± 2.9 months). Background lipid-lowering therapy was given according to local protocols. Lomitapide was commenced with a stepwise dose escalation from 2.5 mg or 5 mg/day; dietary advice and vitamin supplements were provided as per the product label for adults. Laboratory analysis was conducted as part of regular clinical care.ResultsIn the 11 cases, mean baseline LDL-C was 419 ± 74.6 mg/dL and was markedly reduced by lomitapide to a nadir of 176.7 ± 46.3 mg/dL (58.4 ± 6.8% decrease). Six patients achieved recommended target levels for children below 135 mg/dL, five of whom had LA frequency reduced. In one case, LDL-C levels were close to target when lomitapide was started but remained stable despite 75% reduction in LA frequency (from twice weekly to biweekly). Adverse events were mainly gastrointestinal in nature, occurred early in the treatment course and were well managed. Three patients with excursions in liver function tests were managed chiefly without intervention; two patients had decreases in lomitapide dose.ConclusionsLomitapide demonstrated promising effectiveness in paediatric HoFH patients. Adverse events were manageable, and the clinical profile of the drug is apparently similar to that in adult patients.FundingAmryt Pharma.

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Section: Discussionsupporting

confidence: 86%

Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia

et al. 2019

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“…Real et al reported two HoFH brothers (47 and 46 years old) with very premature ASCVD treated with lomitapide over maximum combined LLT and LDL apheresis 32. In the first patient, LDL-C remained close to 130 mg/dL in the interapheresis period.…”

Section: Real-world Clinical Experiencementioning

confidence: 99%

<p>Lomitapide: a review of its clinical use, efficacy, and tolerability</p>

Alonso¹,

Cuevas²,

Mata³

2019

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Lomitapide is an inhibitor of MTP, an enzyme located in the endoplasmic reticulum of hepatocytes and enterocytes. This enzyme is responsible for the synthesis of very low-density lipoproteins in the liver and chylomicrons in the intestine. Lomitapide has been approved by the US Food and Drug Administration, European Medicines Agency, and other regulatory agencies for the treatment of hypercholesterolemia in adult patients with homozygous familial hypercholesterolemia. Clinical trials have shown that lomitapide reduces low-density-lipoprotein cholesterol levels by around 40% in homozygous familial hypercholesterolemia patients on treatment with statins with or without low-density-lipoprotein apheresis, with an acceptable safety and tolerance profile. The most common adverse events are gastrointestinal symptoms that decrease in frequency with long-term treatment, and the increase in liver fat remains stable. This review analyzes the clinical use, efficacy, and tolerability of lomitapide.

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“…The addition of lomitapide powerfully reduced 54% of the LDL-C and 15% of major coronary artery diseases [ 77 ]. Thus, utilizing lomitapide as adjunct therapy can potentially and safely optimize the reduction of LDL-C through genotype-independent effects in FH subjects [ 73 , 79 ].…”

Section: Pharmacogenomics Of Non-statin Lipid-lowering Therapies In Fhmentioning

confidence: 99%

Pharmacogenomics Variability of Lipid-Lowering Therapies in Familial Hypercholesterolemia

Hindi

Alenbawi

Nemer

2021

JPM

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The exponential expansion of genomic data coupled with the lack of appropriate clinical categorization of the variants is posing a major challenge to conventional medications for many common and rare diseases. To narrow this gap and achieve the goals of personalized medicine, a collaborative effort should be made to characterize the genomic variants functionally and clinically with a massive global genomic sequencing of “healthy” subjects from several ethnicities. Familial-based clustered diseases with homogenous genetic backgrounds are amongst the most beneficial tools to help address this challenge. This review will discuss the diagnosis, management, and clinical monitoring of familial hypercholesterolemia patients from a wide angle to cover both the genetic mutations underlying the phenotype, and the pharmacogenomic traits unveiled by the conventional and novel therapeutic approaches. Achieving a drug-related interactive genomic map will potentially benefit populations at risk across the globe who suffer from dyslipidemia.

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Management of homozygous familial hypercholesterolaemia in two brothers

Cited by 7 publications

References 17 publications

Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia

Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia

<p>Lomitapide: a review of its clinical use, efficacy, and tolerability</p>

Pharmacogenomics Variability of Lipid-Lowering Therapies in Familial Hypercholesterolemia

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