Background and aim: Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the LDLRAP1 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. Results: 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). Conclusion: Lomitapide is effective and safe in ARH therapy as well as in classical HoFH.

Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study / 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, ; Italian and European Working Group on Lomitapide in HoFH: Marcello Arca, Marcello.; Bini, Simone; Alessia Di Costanzo, ; D’Erasmo, Laura; Averna, Maurizio; Angelo Baldassare Cefalù, ; Giammanco, Antonina; Pisciotta, Livia; Bertolini, Stefano; Boersma, Eric; Bonomo, Katia; Nota, Fabio; Bucci, Marco; Calabresi, Laura; Pavanello, Chiara; Calabrò, Paolo; Cesaro, Arturo; Cegla, Jaimini; D’Addato, Sergio; Ventura, Fulvio; Daphnis, Eugene; DI TARANTO, MARIA DONATA; Fortunato, Giuliana; Ellis, Avishay; Fimiani, Fabio; Gentile, Marco; Iannuzzo, Gabriella; Kayikcioglu, Meral; Kolovou, Genovefa; Liberopoulos, Evangelos; Littmann, Karin; Martínez-Hervás, Sergio; Montalcini, Tiziana; Puja, Arturo; Real, José; Rutten, Joost; Steward, Kim; Jeanine Roeters van Lennep, ; Sabbà, Carlo; Suppressa, Patrizia; Sampietro, Tiziana; Sbrana, Francesco; Vogt, Anja; Giovanni Battista Vigna, ; Shahenaz, Walji.. - In: FRONTIERS IN GENETICS. - ISSN 1664-8021. - 13:(2022), p. 937750. [10.3389/fgene.2022.937750]

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

Iannuzzo, Gabriella;Maurizio Averna;Maria Donata Di Taranto;Giuliana Fortunato;Marco Gentile;Gabriella Iannuzzo;
2022

Abstract

Background and aim: Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the LDLRAP1 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. Results: 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). Conclusion: Lomitapide is effective and safe in ARH therapy as well as in classical HoFH.
2022
Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study / 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, ; Italian and European Working Group on Lomitapide in HoFH: Marcello Arca, Marcello.; Bini, Simone; Alessia Di Costanzo, ; D’Erasmo, Laura; Averna, Maurizio; Angelo Baldassare Cefalù, ; Giammanco, Antonina; Pisciotta, Livia; Bertolini, Stefano; Boersma, Eric; Bonomo, Katia; Nota, Fabio; Bucci, Marco; Calabresi, Laura; Pavanello, Chiara; Calabrò, Paolo; Cesaro, Arturo; Cegla, Jaimini; D’Addato, Sergio; Ventura, Fulvio; Daphnis, Eugene; DI TARANTO, MARIA DONATA; Fortunato, Giuliana; Ellis, Avishay; Fimiani, Fabio; Gentile, Marco; Iannuzzo, Gabriella; Kayikcioglu, Meral; Kolovou, Genovefa; Liberopoulos, Evangelos; Littmann, Karin; Martínez-Hervás, Sergio; Montalcini, Tiziana; Puja, Arturo; Real, José; Rutten, Joost; Steward, Kim; Jeanine Roeters van Lennep, ; Sabbà, Carlo; Suppressa, Patrizia; Sampietro, Tiziana; Sbrana, Francesco; Vogt, Anja; Giovanni Battista Vigna, ; Shahenaz, Walji.. - In: FRONTIERS IN GENETICS. - ISSN 1664-8021. - 13:(2022), p. 937750. [10.3389/fgene.2022.937750]
File in questo prodotto:
File Dimensione Formato  
fgene-13-937750.pdf

accesso aperto

Licenza: Creative commons
Dimensione 975.41 kB
Formato Adobe PDF
975.41 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/938197
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 5
social impact