The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia – A post-hoc analysis of a Phase 3, single-arm, open-label trial

Autor: S. Di Giacomo, Maurizio Averna, Dirk J. Blom, Daniel J. Rader, G.B. Vigna, H. dT. Theron, Daniel Gaudet, Claudia Stefanutti, Emma A. Meagher, LeAnne Bloedon, Bruce S. Sachais, Adrian David Marais, Prediman K. Shah, Marina Cuchel, A.M.E. du Plessis, Robert A. Hegele, J. Balser, Cesare R. Sirtori
Přispěvatelé: Stefanutti, C., Blom, D., Averna, M., Meagher, E., Theron, H., Marais, A., Hegele, R., Sirtori, C., Shah, P., Gaudet, D., Vigna, G., Sachais, B., Di Giacomo, S., du Plessis, A., Bloedon, L., Balser, J., Rader, D., Cuchel, M.
Rok vydání: 2015
Předmět:
Male
Time Factors
Settore MED/09 - Medicina Interna
Gastroenterology
Microsomal triglyceride transfer protein
chemistry.chemical_compound
Lipoprotein apheresis
Medicine
Hyperlipoproteinemia Type II
Homozygous familial hypercholesterolaemia
Lomitapide
Adult
Anticholesteremic Agents
Benzimidazoles
Biomarkers
Blood Component Removal
Cholesterol
LDL
Combined Modality Therapy
Female
Genetic Predisposition to Disease
Humans
Lipoprotein(a)
Phenotype
Treatment Outcome
Young Adult
Homozygote
Cardiology and Cardiovascular Medicine
biology
Cholesterol
lipids (amino acids
peptides
and proteins)
medicine.medical_specialty
Socio-culturale
Lipoprotein apheresi
Article
LDL
Internal medicine
Post-hoc analysis
business.industry
Endocrinology
Apheresis
chemistry
Concomitant
Adjunctive treatment
biology.protein
business
Zdroj: Atherosclerosis. 240(2):408-414
ISSN: 0021-9150
DOI: 10.1016/j.atherosclerosis.2015.03.014
Popis: ObjectiveLomitapide (a microsomal triglyceride transfer protein inhibitor) is an adjunctive treatment for homozygous familial hypercholesterolaemia (HoFH), a rare genetic condition characterised by elevated low-density lipoprotein-cholesterol (LDL-C), and premature, severe, accelerated atherosclerosis. Standard of care for HoFH includes lipid-lowering drugs and lipoprotein apheresis. We conducted a post-hoc analysis using data from a Phase 3 study to assess whether concomitant apheresis affected the lipid-lowering efficacy of lomitapide.MethodsExisting lipid-lowering therapy, including apheresis, was to remain stable from Week −6 to Week 26. Lomitapide dose was escalated on the basis of individual safety/tolerability from 5 mg to 60 mg a day (maximum). The primary endpoint was mean percent change in LDL-C from baseline to Week 26 (efficacy phase), after which patients remained on lomitapide through Week 78 for safety assessment and further evaluation of efficacy. During this latter period, apheresis could be adjusted. We analysed the impact of apheresis on LDL-C reductions in patients receiving lomitapide.ResultsOf the 29 patients that entered the efficacy phase, 18 (62%) were receiving apheresis at baseline. Twenty-three patients (13 receiving apheresis) completed the Week 26 evaluation. Of the six patients who discontinued in the first 26 weeks, five were receiving apheresis. There were no significant differences in percent change from baseline of LDL-C at Week 26 in patients treated (−48%) and not treated (−55%) with apheresis (p = 0.545). Changes in Lp(a) levels were modest and not different between groups (p = 0.436).ConclusionThe LDL-C lowering efficacy of lomitapide is unaffected by lipoprotein apheresis.
Databáze: OpenAIRE
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