Background: Homozygous familial hypercholesterolemia (HoFH) is a rare life-threatening condition that represents a therapeutic challenge. The vast majority of HoFH patients fail to achieve LDL-C targets when treated with the standard protocol, which associates maximally tolerated dose of lipid-lowering medications with lipoprotein apheresis (LA). Lomitapide is an emerging therapy in HoFH, but its place in the treatment algorithm is disputed because a comparison of its long-term efficacy versus LA in reducing LDL-C burden is not available. We assessed changes in long-term LDL-C burden and goals achievement in two independent HoFH patients’ cohorts, one treated with lomitapide in Italy (n = 30) and the other with LA in France (n = 29). Results: The two cohorts differed significantly for genotype (p = 0.004), baseline lipid profile (p < 0.001), age of treatment initiation (p < 0.001), occurrence of cardiovascular disease (p = 0.003) as well as follow-up duration (p < 0.001). The adjunct of lomitapide to conventional lipid-lowering therapies determined an additional 58.0% reduction of last visit LDL-C levels, compared to 37.1% when LA was added (padj = 0.004). Yearly on-treatment LDL-C < 70 mg/dl and < 55 mg/dl goals were only achieved in 45.5% and 13.5% of HoFH patients treated with lomitapide. The long-term exposure to LDL-C burden was found to be higher in LA than in Lomitapide cohort (13,236.1 ± 5492.1 vs. 11,656.6 ± 4730.9 mg/dL-year respectively, padj = 0.002). A trend towards fewer total cardiovascular events was observed in the Lomitapide than in the LA cohort. Conclusions: In comparison with LA, lomitapide appears to provide a better control of LDL-C in HoFH. Further studies are needed to confirm this data and establish whether this translates into a reduction of cardiovascular risk.

Long-term efficacy of lipoprotein apheresis and lomitapide in the treatment of homozygous familial hypercholesterolemia (HoFH) : a cross-national retrospective survey / L. D'Erasmo, A. Gallo, A.B. Cefalu, A. Di Costanzo, S. Saheb, A. Giammanco, M. Averna, A. Buonaiuto, G. Iannuzzo, G. Fortunato, A. Puja, T. Montalcini, C. Pavanello, L. Calabresi, G.B. Vigna, M. Bucci, K. Bonomo, F. Nota, T. Sampietro, F. Sbrana, P. Suppressa, C. Sabba, F. Fimiani, A. Cesaro, P. Calabro, S. Palmisano, S. D'Addato, L. Pisciotta, S. Bertolini, R. Bittar, O. Kalmykova, S. Beliard, A. Carrie, M. Arca, E. Bruckert. - In: ORPHANET JOURNAL OF RARE DISEASES. - ISSN 1750-1172. - 16:1(2021 Sep), pp. 381.1-381.12. [10.1186/s13023-021-01999-8]

Long-term efficacy of lipoprotein apheresis and lomitapide in the treatment of homozygous familial hypercholesterolemia (HoFH) : a cross-national retrospective survey

C. Pavanello;L. Calabresi;
2021-09

Abstract

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare life-threatening condition that represents a therapeutic challenge. The vast majority of HoFH patients fail to achieve LDL-C targets when treated with the standard protocol, which associates maximally tolerated dose of lipid-lowering medications with lipoprotein apheresis (LA). Lomitapide is an emerging therapy in HoFH, but its place in the treatment algorithm is disputed because a comparison of its long-term efficacy versus LA in reducing LDL-C burden is not available. We assessed changes in long-term LDL-C burden and goals achievement in two independent HoFH patients’ cohorts, one treated with lomitapide in Italy (n = 30) and the other with LA in France (n = 29). Results: The two cohorts differed significantly for genotype (p = 0.004), baseline lipid profile (p < 0.001), age of treatment initiation (p < 0.001), occurrence of cardiovascular disease (p = 0.003) as well as follow-up duration (p < 0.001). The adjunct of lomitapide to conventional lipid-lowering therapies determined an additional 58.0% reduction of last visit LDL-C levels, compared to 37.1% when LA was added (padj = 0.004). Yearly on-treatment LDL-C < 70 mg/dl and < 55 mg/dl goals were only achieved in 45.5% and 13.5% of HoFH patients treated with lomitapide. The long-term exposure to LDL-C burden was found to be higher in LA than in Lomitapide cohort (13,236.1 ± 5492.1 vs. 11,656.6 ± 4730.9 mg/dL-year respectively, padj = 0.002). A trend towards fewer total cardiovascular events was observed in the Lomitapide than in the LA cohort. Conclusions: In comparison with LA, lomitapide appears to provide a better control of LDL-C in HoFH. Further studies are needed to confirm this data and establish whether this translates into a reduction of cardiovascular risk.
Cholesterol burden; Genetic disease; Homozygous hypercholesterolemia; LDL; Lipoprotein apheresis; Lomitapide; Therapeutics
Settore BIO/14 - Farmacologia
Settore MED/09 - Medicina Interna
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/868548
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