• Raul D Santos, Andrea Ruzza, G Kees Hovingh, Albert Wiegman, François Mach, Christopher E Kurtz, Andrew Hamer, Ian Bridges, Andrea Bartuli, Jean Bergeron, Tamás Szamosi, Saikat Santra, Claudia Stefanutti, Olivier S Descamps, Susanne Greber-Platzer, Ilse Luirink, KasteleinJohn J PJJPFrom the Lipid Clinic Heart Institute, University of São Paulo Medical School Hospital and Hospital Israelita Albert Einstein, São Paulo (R.D.S.); Amgen, Thousand Oaks, CA (A.R., C.E.K, A.H.); the Departments of Vascular Medicine (G.K., Daniel Gaudet, and HAUSER-RCT Investigators.
• From the Lipid Clinic Heart Institute, University of São Paulo Medical School Hospital and Hospital Israelita Albert Einstein, São Paulo (R.D.S.); Amgen, Thousand Oaks, CA (A.R., C.E.K, A.H.); the Departments of Vascular Medicine (G.K.H., J.J.P.K.) and Pediatrics (A.W., I.L.), Amsterdam UMC, Amsterdam; the Cardiology Department, Geneva University Hospital, Geneva (F.M.); the Biostatistics Department, Amgen, Cambridge (I.B.), and the Department of Clinical Inherited Metabolic Disorders, Birmingham Children's Hospital, Birmingham (S.S.) - both in the United Kingdom; the Rare Diseases and Clinical Genetics Unit, Academic Pediatric Department, Bambino Gesù Children's Hospital (A.B.), and the Department of Molecular Medicine, Umberto I Hospital, Sapienza University of Rome (C.S.), Rome; the Lipid Clinic, Department of Medicine, Centre Hospitalier Universitaire de Québec-Université Laval, Quebec (J.B.), and the Clinical Lipidology and Rare Lipid Disorders Unit, Community Genomic Medicine Centre and ECOGENE-21, Department of Medicine, Université de Montréal, Chicoutimi, QC (D.G.) - both in Canada; the 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary (T.S.); the Department of Internal Medicine, Centres Hospitaliers Jolimont, La Louvière, Belgium (O.S.D.); and the Division of Pediatric Pulmonology, Allergology, and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (S.G.-P.).
• N. Engl. J. Med. 2020 Oct 1; 383 (14): 1317-1327.

BackgroundEvolocumab, a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9, is widely used in adult patients to lower low-density lipoprotein (LDL) cholesterol levels. Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known.MethodsWe conducted a 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia. Patients 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter (3.4 mmol per liter) or more and a triglyceride level of 400 mg per deciliter (4.5 mmol per liter) or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo. The primary end point was the percent change in LDL cholesterol level from baseline to week 24; key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24.ResultsA total of 157 patients underwent randomization and received evolocumab (104 patients) or placebo (53 patients). At week 24, the mean percent change from baseline in LDL cholesterol level was -44.5% in the evolocumab group and -6.2% in the placebo group, for a difference of -38.3 percentage points (P<0.001). The absolute change in the LDL cholesterol level was -77.5 mg per deciliter (-2.0 mmol per liter) in the evolocumab group and -9.0 mg per deciliter (-0.2 mmol per liter) in the placebo group, for a difference of -68.6 mg per deciliter (-1.8 mmol per liter) (P<0.001). Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups.ConclusionsIn this trial involving pediatric patients with familial hypercholesterolemia, evolocumab reduced the LDL cholesterol level and other lipid variables. (Funded by Amgen; HAUSER-RCT ClinicalTrials.gov number, NCT02392559.).Copyright © 2020 Massachusetts Medical Society.

28 keywords...

hide…