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
Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
Dipartimento di Promozione Della Salute Materno Infantile, Medicina Interna e Specialistica Di Eccellenza "G. D'Alessandro" (PROMISE), Università Degli Studidi Palermo, Palermo, Italy.
Front Genet. 2022 Aug 22;13:937750. doi: 10.3389/fgene.2022.937750. eCollection 2022.
Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the 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. 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). Lomitapide is effective and safe in ARH therapy as well as in classical HoFH.
常染色体隐性高胆固醇血症（ARH）是一种由该基因的致病变异引起的罕见的常染色体隐性低密度脂蛋白（LDL）代谢紊乱疾病。与纯合子家族性高胆固醇血症一样，ARH对传统的降低LDL药物耐药，并导致动脉粥样硬化性心血管疾病（ASCVD）和主动脉瓣狭窄的高风险。洛美他派正在成为经典纯合子家族性高胆固醇血症（HoFH）的一种有效治疗方法，但关于ARH的数据很少。这是对泛欧洲洛美他派研究中纳入的9例ARH患者进行的一项亚组分析。开始使用洛美他派时的年龄为46（四分位间距（IQR），39.0 - 65.5）岁，中位治疗持续时间为31.0（IQR 14.0 - 40.5）个月。基线时，4例（44.4%）患者患有高血压，1例（11.1%）患有糖尿病，2例（22.2%）为现吸烟者，5例（55.5%）报告有ASCVD。基线LDL-C为257.0（IQR，165.3 - 309.2）mg/dL。所有患者均服用他汀类药物加依折麦布，3例接受脂蛋白分离术（LA），1例还接受前蛋白转化酶枯草溶菌素/kexin 9型抑制剂（PCSK9i）。添加洛美他派（平均剂量，10 mg）导致治疗期间LDL-C的中位数达到101.7 mg/dL（IQR，71.3 - 138.3；较基线降低60.4%），最佳LDL-C值为68.0 mg/dL（IQR，43.7 - 86.7；较基线降低73.5%）。随访期间，1例患者停用了PCSK9i和LA。1例患者报告发生了ASCVD事件复发。治疗期间天冬氨酸转氨酶和丙氨酸转氨酶的中位数分别为31.1（IQR，22.6 - 48.3）U/L和31.1（IQR，27.2 - 53.8）U/L。在6例可进行肝脏硬度扫描检查的ARH患者中，最后一次就诊时记录的肝脏硬度值在正常范围内（中位数，4.7 KPa；IQR，3.6 - 5.3 KPa）。洛美他派在ARH治疗以及经典HoFH中都是有效且安全的。
