Frontiers in Genetics (Aug 2022)

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

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

DOI
https://doi.org/10.3389/fgene.2022.937750
Journal volume & issue
Vol. 13

Abstract

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Backgroundand 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.

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