Tawfeg Ben-Omran, Luis Masana, Genovefa Kolovou, Gema Ariceta, F. Javier Nóvoa, Allan M. Lund, Martin P. Bogsrud, María Araujo, Osamah Hussein, Daiana Ibarretxe, Rosa M. Sanchez-Hernández and Raul D. Santos contributed equally to this work.
To view enhanced digital features for this article go to https://doi.org/10.6084/m9.figshare.8076275.
Homozygous 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.
This 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.
In 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.
Lomitapide 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.
Cuchel M, Bruckert E, Ginsberg HN, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35(32):2146–57. https://doi.org/10.1093/eurheartj/ehu274. CrossRef
Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478–3490a. https://doi.org/10.1093/eurheartj/eht273. CrossRef
Humphries SE, Cooper J, Dale P, Ramaswami U, FH Paediatric Register Steering Group. The UK paediatric familial hypercholesterolaemia register: statin-related safety and 1-year growth data. J Clin Lipidol. 2018;12(1):25–32. https://doi.org/10.1016/j.jacl.2017.11.005. CrossRef
Santos RD, Gidding SS, Hegele RA, et al. Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel. Lancet Diabetes Endocrinol. 2016;4(10):850–61. https://doi.org/10.1016/S2213-8587(16)30041-9. CrossRef
Stefanutti C, Di Giacomo S, Vivenzio A, et al. Low-density lipoprotein apheresis in a patient aged 3.5 years. Acta Paediatr. 2001;90(6):694–701. CrossRef
Gagné C, Gaudet D, Bruckert E, Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation. 2002;105(21):2469–75. https://doi.org/10.1161/01.cir.0000018744.58460.62. CrossRef
Hudgins LC, Kleinman B, Scheuer A, White S, Gordon BR. Long-term safety and efficacy of low-density lipoprotein apheresis in childhood for homozygous familial hypercholesterolemia. Am J Cardiol. 2008;102(9):1199–204. https://doi.org/10.1016/j.amjcard.2008.06.049. CrossRef
Thompson GR, Barbir M, Davies D, et al. Efficacy criteria and cholesterol targets for LDL apheresis. Atherosclerosis. 2010;208(2):317–21. https://doi.org/10.1016/j.atherosclerosis.2009.06.010. CrossRef
Kroon AA, van’t Hof MA, Demacker PN, Stalenhoef AF. The rebound of lipoproteins after LDL-apheresis. Kinetics and estimation of mean lipoprotein levels. Atherosclerosis. 2000;152(2):519–26. https://doi.org/10.1016/s0021-9150(00)00371-3. CrossRef
Luirink IK, Determeijer J, Hutten BA, et al. Efficacy and safety of lipoprotein apheresis in children with homozygous familial hypercholesterolemia: a systematic review. J Clin Lipidol. 2018. https://doi.org/10.1016/j.jacl.2018.10.011.
Thompson GR, Catapano A, Saheb S, et al. Severe hypercholesterolaemia: therapeutic goals and eligibility criteria for LDL apheresis in Europe. Curr Opin Lipidol. 2010;21(6):492–8. https://doi.org/10.1097/MOL.0b013e3283402f53. CrossRef
Bruckert E, Saheb S, Bonté JR, Coudray-Omnès C. Daily life, experience and needs of persons suffering from homozygous familial hypercholesterolaemia: insights from a patient survey. Atheroscler Suppl. 2014;15:46–51. CrossRef
Aegerion Pharmaceuticals Inc. Juxtapid prescribing information 2013. http://www.juxtapid.com/sites/default/files/downloads/Prescribing_Information.pdf. Accessed 3 May 2019.
Amryt Pharmaceuticals DAC. Lojuxta summary of product characteristics 2015. https://www.medicines.org.uk/emc. Accessed 3 May 2019.
Amryt Pharmaceuticals DAC. Lojuxta summary of product characteristics 2017. https://www.medicines.org.uk/emc. Accessed 3 May 2019.
Cuchel M, Blom DJ, Averna M, et al. Sustained LDL-C lowering and stable hepatic fat levels in patients with homozygous familial hypercholesterolemia treated with the microsomal transfer protein inhibitor lomitapide: results of an ongoing long-term extension study. American Heart Association Scientific Sessions, Dallas, Texas. 2013. Abstract 16516.
Underberg J, Cannon CP, Larrey D, Makris L, Jurecka A, Blom D. Long-term safety and efficacy of lomitapide in patients With homozygous familial hypercholesterolemia: three-year data from the Lomitapide Observational orldwide Evaluation Registry (LOWER). ACC18 67th Annual Scientific Session and Expo, 10–12 March, Orlando, FL. 2018.
Blom DJ, Averna MR, Meagher EA, et al. Long-term efficacy and safety of the microsomal triglyceride transfer protein inhibitor lomitapide in patients with homozygous familial hypercholesterolemia. Circulation. 2017;136(3):332–5. https://doi.org/10.1161/circulationaha.117.028208. CrossRef
Chacra AP, Ferrari MC, Rocha VZ, Santos RD. Case report: the efficiency and safety of lomitapide in a homozygous familial hypercholesterolemic child. J Clin Lipidol. 2019. https://doi.org/10.1016/j.jacl.2019.03.001 (in press).
Raal FJ, Hovingh GK, Blom D, et al. Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study. Lancet Diabetes Endocrinol. 2017. https://doi.org/10.1016/s2213-8587(17)30044-x.
Roeters van Lennep J, Averna M, Alonso R. Treating homozygous familial hypercholesterolemia in a real-world setting: experiences with lomitapide. J Clin Lipidol. 2015;9(4):607–17. https://doi.org/10.1016/j.jacl.2015.05.001. CrossRef
Cuchel M, Meagher EA, du Toit Theron H, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet. 2013;381(9860):40–6. https://doi.org/10.1016/S0140-6736(12)61731-0. CrossRef
Averna M, Cefalu AB, Stefanutti C, Di Giacomo S, Sirtori CR, Vigna GB. Individual analysis of patients with HoFH participating in a phase 3 trial with lomitapide: the Italian cohort. Nutr Metab Cardiovasc Dis. 2015;26(1):36–44. https://doi.org/10.1016/j.numecd.2015.11.001. CrossRef
Moriarty PM, Parhofer KG, Babirak SP, et al. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur Heart J. 2016. https://doi.org/10.1093/eurheartj/ehw388.
Real J, Arbona C, Goterris R, Ascaso JF. Management of homozygous familial hypercholesterolaemia in two brothers. BMJ Case Rep 2018. 2018. https://doi.org/10.1136/bcr-2017-222155.
- Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia
F. Javier Nóvoa
Allan M. Lund
Martin P. Bogsrud
Rosa M. Sanchez-Hernández
Raul D. Santos
- Springer Healthcare
Advances in Therapy
Print ISSN: 0741-238X
Elektronische ISSN: 1865-8652
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II