{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T03:40:55Z","timestamp":1769830855283,"version":"3.49.0"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background<\/jats:bold><jats:bold>and aim:<\/jats:bold> Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the <jats:italic>LDLRAP1<\/jats: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.<\/jats:p><jats:p><jats:bold>Results:<\/jats: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\u201365.5)\u00a0years, with a median treatment duration of 31.0 (IQR 14.0\u201340.5)\u00a0months. 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\u2013309.2)\u00a0mg\/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\u00a0mg) resulted in the achievement of a median on-treatment LDL-C of 101.7\u00a0mg\/dL (IQR, 71.3\u2013138.3; 60.4% reduction from baseline), with a best LDL-C value of 68.0\u00a0mg\/dL (IQR, 43.7\u201386.7; 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\u201348.3)\u00a0U\/L and 31.1 (IQR, 27.2\u201353.8)\u00a0U\/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\u00a0KPa; IQR, 3.6\u20135.3\u00a0KPa).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Lomitapide is effective and safe in ARH therapy as well as in classical HoFH.<\/jats:p>","DOI":"10.3389\/fgene.2022.937750","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T08:18:31Z","timestamp":1661329111000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study"],"prefix":"10.3389","volume":"13","author":[{"given":"Laura","family":"D\u2019Erasmo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonina","family":"Giammanco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Suppressa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Pavanello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Iannuzzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Di Costanzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Tramontano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilenia","family":"Minicocci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Bini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Vogt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim","family":"Stewards","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanine","family":"Roeters Van Lennep","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Bertolini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcello","family":"Arca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Italian and European Working Group on Lomitapide in HoFH","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.atherosclerosis.2020.08.027","article-title":"Homozygous Familial Hypercholesterolemia in Italy: Clinical and Molecular Features","volume":"312312","author":"Bertolini","year":"2020","journal-title":"Atherosclerosis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/J.HFC.2021.07.008","article-title":"New Frontiers in the Treatment of Homozygous Familial Hypercholesterolemia","volume":"18","author":"Cesaro","year":"2022","journal-title":"Heart Fail. 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