Pediatric experience with mipomersen as adjunctive therapy for homozygous familial hypercholesterolemia
| Autor: | John J.P. Kastelein, Marjet J. Braamskamp, Charlotte Sensinger, Frederick J. Raal, Sheryl Selvey |
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| Přispěvatelé: | Amsterdam Cardiovascular Sciences, Amsterdam Gastroenterology Endocrinology Metabolism, General Paediatrics, Vascular Medicine |
| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Apolipoprotein B Adolescent Endocrinology Diabetes and Metabolism Lipoproteins Mipomersen Hypercholesterolemia Oligonucleotides Familial hypercholesterolemia 030204 cardiovascular system & hematology Placebo Pediatrics law.invention Hyperlipoproteinemia Type II 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Internal medicine medicine Internal Medicine Humans Drug Interactions Adverse effect Child Nutrition and Dietetics biology business.industry Anticholesteremic Agents Homozygote medicine.disease Surgery Clinical trial 030104 developmental biology Cholesterol Cohort biology.protein Female lipids (amino acids peptides and proteins) Safety business Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of clinical lipidology, 10(4), 860-869. Elsevier BV |
| ISSN: | 1933-2874 |
| DOI: | 10.1016/j.jacl.2016.02.018 |
| Popis: | Background Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited condition resulting in severely elevated low-density lipoprotein cholesterol levels (LDL-C) leading to premature cardiovascular disease and, often, death. Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein B (apo B) synthesis, lowering LDL-C levels. Mipomersen has demonstrated efficacy in adult HoFH patients, possibly providing a therapeutic option for pediatric patients. Study objectives were to summarize mipomersen efficacy and safety in the pediatric cohort of a phase 3 randomized controlled trial (RCT) and subsequent open-label extension study (OLE). Methods Seven patients aged 12–18 years were randomized to 200-mg mipomersen or placebo weekly (26 weeks) and received mipomersen in the OLE (52 or 104 weeks). Plasma LDL-C and apo B concentrations and adverse events were assessed. Results All pediatric patients completed the RCT and entered OLE. The 3 mipomersen patients in the RCT experienced mean reductions from baseline to RCT end of 42.7% and 46.1% for LDL-C and apo B, respectively. Of the 4 placebo patients, 3 responded well to mipomersen during OLE, with reductions in LDL-C of 26.5%–42.1%. Three patients completed OLE treatment, and 4 patients discontinued therapy due to adverse events. Lipid level fluctuations were observed and were likely due to poor compliance. Conclusions Long-term mipomersen treatment was successful regarding efficacy parameters for pediatric HoFH patients. The safety profile was consistent with other phase 3 clinical trials. Long-term compliance was an issue. Measures supporting adherence should be encouraged. |
| Databáze: | OpenAIRE |
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