AUTHOR=D’Erasmo Laura , Giammanco Antonina , Suppressa Patrizia , Pavanello Chiara , Iannuzzo Gabriella , Di Costanzo Alessia , Tramontano Daniele , Minicocci Ilenia , Bini Simone , Vogt Anja , Stewards Kim , Roeters Van Lennep Jeanine , Bertolini Stefano , Arca Marcello ,  the Italian and European Working Group on Lomitapide in HoFH , Arca Marcello , Averna Maurizio , Bertolini Stefano , Bini Simone , Boersma Eric , Bonomo Katia , Bucci Marco , Calabresi Laura , Calabrò Paolo , Cefalù Angelo Baldassare , Cegla Jaimini , Cesaro Arturo , D’Addato Sergio , Daphnis Eugene , Di Costanzo Alessia , D’Erasmo Laura , Di Taranto Maria Donata , Ellis Avishay , Fimiani Fabio , Fortunato Giuliana , Giammanco Antonina , Gentile Marco , Iannuzzo Gabriella , Kayikcioglu Meral , Kolovou Genovefa , Liberopoulos Evangelos , Littmann Karin , Martínez-Hervás Sergio , Montalcini Tiziana , Nota Fabio , Pavanello Chiara , Pisciotta Livia , Puja Arturo , Real Giovanni José , Roeters van Lennep Jeanine , Rutten Joost , Sabbà Carlo , Sampietro Tiziana , Sbrana Francesco , Steward Kim , Suppressa Patrizia , Ventura Fulvio , Vigna Battista , Vogt Anja , Walji Shahenaz 

TITLE=Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.937750

DOI=10.3389/fgene.2022.937750

ISSN=1664-8021

ABSTRACT=<p><bold>Background</bold><bold>and aim:</bold> Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the <italic>LDLRAP1</italic> gene. Like homozygous familial hypercholesterolemia, ARH is resistant to conventional LDL-lowering medications and causes a high risk of atherosclerotic cardiovascular diseases (ASCVDs) and aortic valve stenosis. Lomitapide is emerging as an efficacious therapy in classical HoFH, but few data are available for ARH.</p><p><bold>Results:</bold> This is a subanalysis carried out on nine ARH patients included in the Pan-European Lomitapide Study. The age at starting lomitapide was 46 (interquartile range (IQR), 39.0–65.5) years, with a median treatment duration of 31.0 (IQR 14.0–40.5) months. At baseline, four (44.4%) patients had hypertension, one (11.1%) had diabetes mellitus, two (22.2%) were active smokers, and five (55.5%) reported ASCVD. The baseline LDL-C was 257.0 (IQR, 165.3–309.2) mg/dL. All patients were on statins plus ezetimibe, three were receiving Lipoprotein apheresis (LA), and one was also receiving proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i). The addition of lomitapide (mean dose, 10 mg) resulted in the achievement of a median on-treatment LDL-C of 101.7 mg/dL (IQR, 71.3–138.3; 60.4% reduction from baseline), with a best LDL-C value of 68.0 mg/dL (IQR, 43.7–86.7; 73.5% reduction from baseline). During follow-up, one patient stopped both PCSK9i and LA. Recurrence of ASCVD events was reported in one patient. The median on-treatment aspartate transaminase and alanine transaminase values were 31.1 (IQR, 22.6–48.3) U/L and 31.1 (IQR, 27.2–53.8) U/L, respectively. Among six ARH patients with available fibroscan examination, liver stiffness values recorded at the last visit were within the normal range (median, 4.7 KPa; IQR, 3.6–5.3 KPa).</p><p><bold>Conclusion:</bold> Lomitapide is effective and safe in ARH therapy as well as in classical HoFH.</p>