Lomitapide for treatment of homozygous familial hypercholesterolemia: The Québec experience

Aljenedil, Sumayah; Alothman, Latifah; Belanger, Anne-Marie; Brown, Leslie; Lahijanian, Zubin; Bergeron, Jean; Couture, Patrick; Baass, Alexis; Ruel, Isabelle L.; Brisson, Diane; Khoury, Étienne; Gaudet, Daniel; Genest, Jacques

doi:10.1016/j.atherosclerosis.2020.07.028

Cited by 16 publications

(20 citation statements)

References 38 publications

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“…1 while baseline characteristics of patients are presented in Table 1 (Ref. [19,21,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]).…”

Section: Resultsmentioning

confidence: 99%

“…In the study, six patients were treated for more than two years. Aljenedil et al [28] reported that the twelve HoFH patients in the study had an average age of 44 ± 18 years. All the twelve patients were treated with statins and ezetimibe, while 5 pa-Fig.…”

Section: Adult Hofh Patientsmentioning

confidence: 87%

“…CVD complications, lomitapiderelated adverse events (AEs) were evaluated as safety outcomes (Table 4, Ref. [19,21,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]).…”

Section: Efficacy and Safety Outcomesmentioning

confidence: 99%

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Efficacy and Safety of Lomitapide in Homozygous Familial Hypercholesterolaemia: A Systematic Review

Wei¹,

Hu²,

Li³

et al. 2022

Rev. Cardiovasc. Med.

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Background: Homozygous familial hypercholesterolaemia (HoFH) patients have little or no low-density lipoprotein receptor (LDLR) function. HMG-CoA (3-hydroxy-3-methyl glutaryl coenzyme A) reductase inhibitors (statins) and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have limited lipid-lowering effects, therefore, there is an urgent need to develop new HoFH treatments. In 2012, the US Food and Drug Administration (FDA) approved the administration of lomitapide for lowering low-density lipoprotein cholesterol (LDL-C) levels. However, lomitapide is associated with various gastrointestinal disorders, elevated hepatic alanine aminotransferase (ALT) levels and other adverse reactions, thus, its long-term efficacy and safety in pediatrics and adults should be evaluated. A systematic review conducted in 2017 reported the efficacy and safety of lomitapide in Family hypercholesterolaemia (FH) patients. In this systematic review, we elucidate on the efficacy and safety of lomitapide in HoFH patients. Methods: A search was conducted in PubMed, Embase, Web of Science and Cochrane library databases to identify valid studies involving lomitapide-treated HoFH patients published before 11th August 2021. Results: A total of 18 clinical studies involving 120 lomitapide-treated HoFH patients were identified. Lomitapide significantly suppressed LDL-C levels in HoFH patients. Clinical manifestations for lomitapide in children were comparable to those in adults. The most common adverse events were gastrointestinal disturbances and elevated ALT levels. However, most patients tolerated the treatment-associated adverse reactions. Low-fat diets and drug dose adjustments were appropriate measures for controlling the treatment-associated adverse reactions. Conclusions: In pediatric and adult HoFH patients, lomitapide significantly suppresses LDL-C levels, therefore, it is an important option for HoFH treatment. The most common adverse events of lomitapide treatment include gastrointestinal disorders and elevated hepatic ALT levels. Despite the limitations, lomitapide is feasible for long-term treatment of HoFH patients, with dietary and safety monitoring. Registration Number in PROSPERO: CRD42021284425.

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“…1 while baseline characteristics of patients are presented in Table 1 (Ref. [19,21,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]).…”

Section: Resultsmentioning

confidence: 99%

Section: Adult Hofh Patientsmentioning

confidence: 87%

See 1 more Smart Citation

Efficacy and Safety of Lomitapide in Homozygous Familial Hypercholesterolaemia: A Systematic Review

Wei¹,

Hu²,

Li³

et al. 2022

Rev. Cardiovasc. Med.

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“…Lomitapide is an inhibitor of a microsomal triglyceride transfer protein that lowers hepatic low-density lipoprotein cholesterol production, as new therapeutic modalities treating homozygous familial hypercholesterolemia. 33 , 34 Mipomersen decreases the levels of apolipoprotein B, low-density lipoprotein non-high-density lipoprotein cholesterol, and total cholesterol, which are used in patients with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering medications. 34 , 35 For C0026705 (mucopolysaccharidosis II), the significant association with DB00090 (laronidase) is successfully identified by HeTDR.…”

Section: Resultsmentioning

confidence: 99%

HeTDR: Drug repositioning based on heterogeneous networks and text mining

Jin

Niu²,

Jiang

et al. 2021

Patterns

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“…[119][120][121] PCSK9 inhibitors, however, require some residual LDL receptor bioavailability and are therefore less effective or non-effective in homozygous FH (HoFH) patients. For HoFH and refractory FH, LDL receptor-independent agents have been developed, including lomitapide, a microsomal triglyceride transfer protein (MTTP) inhibitor, [122][123][124] and evinacumab, an Angiopoietin-like 3 (ANGPTL-3) inhibitor. [125][126][127] Given the prevalence of FH in SLSJ, the use of expensive therapies such as Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lomitapide or evinacumab might constitute an important socioeconomic hurdle.…”

Section: Familial Hypercholesterolaemia (Fh Mim 143890)mentioning

confidence: 99%

Genetic burden linked to founder effects in Saguenay–Lac-Saint-Jean illustrates the importance of genetic screening test availability

et al. 2021

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The Saguenay–Lac-Saint-Jean (SLSJ) region located in the province of Quebec was settled in the 19th century by pioneers issued from successive migration waves starting in France in the 17th century and continuing within Quebec until the beginning of the 20th century. The genetic structure of the SLSJ population is considered to be the product a triple founder effect and is characterised by a higher prevalence of some rare genetic diseases. Several studies were performed to elucidate the historical, demographic and genetic background of current SLSJ inhabitants to assess the origins of these rare disorders and their distribution in the population. Thanks to the development of new sequencing technologies, the genes and the variants responsible for the most prevalent conditions were identified. Combined with other resources such as the BALSAC population database, identifying the causal genes and the pathogenic variants allowed to assess the impacts of some of these founder mutations on the population health and to design precision medicine public health strategies based on carrier testing. Furthermore, it stimulated the establishment of many public programmes.We report here a review and an update of a subset of inherited disorders and founder mutations in the SLSJ region. Data were collected from published scientific sources. This work expands the knowledge about the current frequencies of these rare disorders, the frequencies of other rare genetic diseases in this population, the relevance of the carrier tests offered to the population, as well as the current available treatments and research about future therapeutic avenues for these inherited disorders.

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Lomitapide for treatment of homozygous familial hypercholesterolemia: The Québec experience

Cited by 16 publications

References 38 publications

Efficacy and Safety of Lomitapide in Homozygous Familial Hypercholesterolaemia: A Systematic Review

Efficacy and Safety of Lomitapide in Homozygous Familial Hypercholesterolaemia: A Systematic Review

HeTDR: Drug repositioning based on heterogeneous networks and text mining

Genetic burden linked to founder effects in Saguenay–Lac-Saint-Jean illustrates the importance of genetic screening test availability

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