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

• Published in: Orphanet journal of rare diseases 2021-09, Vol.16 (1), p.1-381, Article 381
• Main Authors: D'Erasmo, Laura, Gallo, Antonio, Cefalù, Angelo Baldassare, Di Costanzo, Alessia, Saheb, Samir, Giammanco, Antonina, Averna, Maurizio, Buonaiuto, Alessio, Iannuzzo, Gabriella, Fortunato, Giuliana, Puja, Arturo, Montalcini, Tiziana, Pavanello, Chiara, Calabresi, Laura, Vigna, Giovanni Battista, Bucci, Marco, Bonomo, Katia, Nota, Fabio, Sampietro, Tiziana, Sbrana, Francesco, Suppressa, Patrizia, Sabbà, Carlo, Fimiani, Fabio, Cesaro, Arturo, Calabrò, Paolo, Palmisano, Silvia, D'Addato, Sergio, Pisciotta, Livia, Bertolini, Stefano, Bittar, Randa, Kalmykova, Olga, Béliard, Sophie, Carrié, Alain, Arca, Marcello, Bruckert, Eric
• Format: Article
• Language: English
• Subjects: Apheresis; Blood lipoproteins; Cardiovascular diseases; Care and treatment; Cholesterol; Ethnicity; Gender; Genetic disease; Genotype & phenotype; Genotypes; Health aspects; Homozygous hypercholesterolemia; Hypercholesterolemia; LDL; Life Sciences; Lipids; Lipoprotein apheresis; Lipoproteins; Lomitapide; Low density lipoprotein; Medical research; Mutation; Patient outcomes; Patients; Proteolipids; Rare diseases; Therapeutics
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-021-01999-8

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). 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 (p.sub.adj = 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 [+ or -] 5492.1 vs. 11,656.6 [+ or -] 4730.9 mg/dL-year respectively, p.sub.adj = 0.002). A trend towards fewer total cardiovascular events was observed in the Lomitapide than in the LA cohort. 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.