Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension

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art_SANTOS_Longterm_efficacy_and_safety_of_mipomersen_in_patients_2015.PDF (649.95 KB)
Citações na Scopus
113
Tipo de produção
article
Data de publicação
2015
Editora
OXFORD UNIV PRESS
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
DUELL, P. Barton
EAST, Cara
GUYTON, John R.
MORIARTY, Patrick M.
CHIN, Wai
MITTLEMAN, Robert S.
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
EUROPEAN HEART JOURNAL, v.36, n.9, p.566-575, 2015
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Aims To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. Methods and results A planned interim analysis of an ongoing, open-label extension trial in patients (n = 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n = 130), 52 (n = 111), 76 (n = 66), and 104 (n = 53) were -28, -27, -27, and -28%; and in apolipoprotein B -29, -28, -30, and 231%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6-12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Conclusion Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations.
Palavras-chave
hypercholesterolaemia, Hypercholesterolaemia, Lipid-lowering, Adverse events, Long-term safety
URI
https://observatorio.fm.usp.br/handle/OPI/9728
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - ODS/03