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

Laura D’erasmo (1, 2, 3) , Antonio Gallo (2, 4) , Angelo Baldassare Cefalù (5) , Alessia Di Costanzo (1) , Samir Saheb (2, 3) , Antonina Giammanco (5) , Maurizio Averna (5) , Alessio Buonaiuto (6) , Gabriella Iannuzzo (6) , Giuliana Fortunato (6, 7) , Arturo Puja (8) , Tiziana Montalcini (8) , Chiara Pavanello (9) , Laura Calabresi (9) , Giovanni Battista Vigna (10) , Marco Bucci (11) , Katia Bonomo (12) , Fabio Nota (12) , Tiziana Sampietro (13) , Francesco Sbrana (13) , Patrizia Suppressa , Carlo Sabbà , Fabio Fimiani (14) , Arturo Cesaro (14) , Paolo Calabrò (14) , Silvia Palmisano (15) , Sergio D’addato (15) , Livia Pisciotta (16, 17) , Stefano Bertolini (16, 17) , Randa Bittar (18, 2) , Olga Kalmykova (2, 3) , Sophie Béliard (19, 20) , Alain Carrié (18, 2) , Marcello Arca (1) , Eric Bruckert (2, 3)

1 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
2 CHU Pitié-Salpêtrière [AP-HP]
3 SU - Sorbonne Université
4 LIB - Laboratoire d'Imagerie Biomédicale
5 Università degli studi di Palermo - University of Palermo
6 University of Naples Federico II = Università degli studi di Napoli Federico II
7 CEINGE - Biotecnologie Avanzate
8 UMG - Università degli Studi "Magna Graecia" di Catanzaro = University of Catanzaro
9 UNIMI - Università degli Studi di Milano = University of Milan
10 UniFE - Università degli Studi di Ferrara = University of Ferrara
11 Ud'A - Università degli studi "G. d'Annunzio" Chieti-Pescara [Chieti-Pescara]
12 Ospedale San Luigi Gonzaga
13 Fondazione Toscana Gabriele Monasterio
14 University of the Study of Campania Luigi Vanvitelli
15 Policlinico S. Orsola-malpighi
16 UniGe - Università degli studi di Genova = University of Genoa
17 Ospedale Policlinico San Martino [Genoa]
18 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
19 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
20 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]

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 ( p 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 ± 5492.1 vs. 11,656.6 ± 4730.9 mg/dL-year respectively, p adj = 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.

Keywords: Cholesterol burden; Genetic disease; Homozygous hypercholesterolemia; LDL; Lipoprotein apheresis; Lomitapide; Therapeutics

Domains: Life Sciences [q-bio]

Laura D’erasmo, Antonio Gallo, Angelo Baldassare Cefalù, Alessia Di Costanzo, Samir Saheb, et al.. Long-term efficacy of lipoprotein apheresis and lomitapide in the treatment of homozygous familial hypercholesterolemia (HoFH): a cross-national retrospective survey. Orphanet Journal of Rare Diseases, 2021, 16 (1), pp.381. ⟨10.1186/s13023-021-01999-8⟩. ⟨hal-03653394⟩