Evinacumab in Patients with Refractory Hypercholesterolemia
| Autor: | Yuping Dong, Robert Hamlin, Daniel Gaudet, Erik S.G. Stroes, Lesley J. Burgess, Robert Pordy, Nagwa Khilla, Shazia Ali, C. Ebenbichler, Seth J. Baum, Robert S. Rosenson, Vladimir Son |
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| Přispěvatelé: | Experimental Vascular Medicine, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male medicine.medical_specialty Injections Subcutaneous Evinacumab Drug Resistance 030204 cardiovascular system & hematology Antibodies Monoclonal Humanized Gastroenterology Drug Administration Schedule law.invention Hyperlipoproteinemia Type II 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Double-Blind Method Randomized controlled trial Refractory law Internal medicine medicine Humans In patient 030212 general & internal medicine Infusions Intravenous Angiopoietin-Like Protein 3 Cholesterol business.industry Anticholesteremic Agents Antibodies Monoclonal Cholesterol LDL General Medicine Middle Aged Clinical trial Angiopoietin-like Proteins chemistry Multicenter study Female lipids (amino acids peptides and proteins) business Lipoprotein |
| Zdroj: | New England journal of medicine, 383(24), 2307-2319. Massachussetts Medical Society |
| ISSN: | 1533-4406 0028-4793 0317-5367 |
| Popis: | Patients with refractory hypercholesterolemia, who have high low-density lipoprotein (LDL) cholesterol levels despite treatment with lipid-lowering therapies at maximum tolerated doses, have an increased risk of atherosclerosis. In such patients, the efficacy and safety of subcutaneous and intravenous evinacumab, a fully human monoclonal antibody against angiopoietin-like 3, are not known.In this double-blind, placebo-controlled, phase 2 trial, we enrolled patients with or without heterozygous familial hypercholesterolemia who had refractory hypercholesterolemia, with a screening LDL cholesterol level of 70 mg per deciliter or higher with atherosclerosis or of 100 mg per deciliter or higher without atherosclerosis. Patients were randomly assigned to receive subcutaneous or intravenous evinacumab or placebo. The primary end point was the percent change from baseline in the LDL cholesterol level at week 16 with evinacumab as compared with placebo.In total, 272 patients were randomly assigned to the following groups: subcutaneous evinacumab at a dose of 450 mg weekly (40 patients), 300 mg weekly (43 patients), or 300 mg every 2 weeks (39 patients) or placebo (41 patients); or intravenous evinacumab at a dose of 15 mg per kilogram of body weight every 4 weeks (39 patients) or 5 mg per kilogram every 4 weeks (36 patients) or placebo (34 patients). At week 16, the differences in the least-squares mean change from baseline in the LDL cholesterol level between the groups assigned to receive subcutaneous evinacumab at a dose of 450 mg weekly, 300 mg weekly, and 300 mg every 2 weeks and the placebo group were -56.0, -52.9, and -38.5 percentage points, respectively (P0.001 for all comparisons). The differences between the groups assigned to receive intravenous evinacumab at a dose of 15 mg per kilogram and 5 mg per kilogram and the placebo group were -50.5 percentage points (P0.001) and -24.2 percentage points, respectively. The incidence of serious adverse events during the treatment period ranged from 3 to 16% across trial groups.In patients with refractory hypercholesterolemia, the use of evinacumab significantly reduced the LDL cholesterol level, by more than 50% at the maximum dose. (Funded by Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT03175367.). |
| Databáze: | OpenAIRE |
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