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Dyslipidemia
Published in Jahangir Moini, Matthew Adams, Anthony LoGalbo, Complications of Diabetes Mellitus, 2022
Jahangir Moini, Matthew Adams, Anthony LoGalbo
To reduce triglycerides, omega-3 fatty acids can be effective in high doses – 1–6 g per day of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). These fatty acids are active ingredients in both ocean fish oil and omega-3 supplements. Adverse effects include diarrhea and eructation, but these can be reduced if the supplements not all taken during one meal. Prescription omega-3 fatty acids are used for triglyceride levels above 500 mg/dL (5.65 mmol/L). In some countries, the apo CIII inhibitor called volanesorsen is available, and lowers severely elevated triglyceride levels, such as in people with lipoprotein lipase deficiency. The drug is given as a once-weekly injection.
Recent advances in treating hypertriglyceridemia in patients at high risk of cardiovascular disease with apolipoprotein C-III inhibitors
Published in Expert Opinion on Pharmacotherapy, 2023
Catherine M Spagnuolo, Robert A Hegele
Clinical trials to date show that volanesorsen, olezarsen, and ARO-APOC3 produce similar statistically significant reductions in apo C-III and TG levels, with minimal adverse effects. Evidence to date suggests olezarsen or ARO-APOC3 may be the preferable agents for apo C-III inhibition over volanesorsen given no observed drug-induced thrombocytopenia and no associated increase in LDL-C. Although volanesorsen-induced thrombocytopenia was noted in clinical trials, severe thrombocytopenia with platelet counts <25 000 per microL were observed in only a small percentage of patients, and the effect was reversible with recovered platelet counts soon after stopping the drug. In Europe, this adverse effect was considered to be offset by the potential for large benefits of volanesorsen among FCS patients specifically in reducing the risk of acute pancreatitis.
Evaluation of efficacy and safety of antisense inhibition of apolipoprotein C-III with volanesorsen in patients with severe hypertriglyceridemia
Published in Expert Opinion on Pharmacotherapy, 2020
Laura D’Erasmo, Antonio Gallo, Alessia Di Costanzo, Eric Bruckert, Marcello Arca
The APPROACH study [59] is a recently completed multicenter, randomized, placebo-controlled, double-blind study evaluating the efficacy and safety of volanesorsen 300 mg subcutaneously once a week as compared with placebo in patients older than 18 years of age who had FCS. Patients were eligible to participate if FCS was confirmed either by genetic testing or by documentation of low LPL activity (levels <20% of the normal range) and if fasting TG levels were at or above 750 mg/dL (8.48 mmol/L). Genetic confirmation of the syndrome was based on the detection of homozygosity, compound heterozygosity, or double heterozygosity for known loss-of-function mutations in LPL, APOC2, APOA5, GPIHBP1, or LMF1 genes. Alternatively, patients were eligible if their post-heparin LPL activity, measured in a central laboratory, was less than 20% of the normal range. Enrollment of patients without a documented history of previous pancreatitis was capped at 28% of the total cohort. After a 6-week diet stabilization run-in period during which patients were asked to follow a diet that included less than 20 g of fat per day, eligible patients were randomly assigned in a 1:1 ratio to volanesorsen at a dose of 300 mg SC per week or placebo, with stratification according to history or no history of pancreatitis and according to receipt or no receipt of concurrent fibrates, prescription n − 3 fatty acids, or both. Volanesorsen or placebo was administered as a single subcutaneous injection once a week for 52 weeks.
Estimating health state utilities associated with a rare disease: familial chylomicronemia syndrome (FCS)
Published in Journal of Medical Economics, 2020
Louis S. Matza, Glenn A. Phillips, Timothy A. Howell, Nicole Ciffone, Zahid Ahmad
One rare disease that will soon require economic modeling is familial chylomicronemia syndrome (FCS). This genetic disorder is most commonly linked to mutations in the gene encoding lipoprotein lipase (LPL), an enzyme that breaks down chylomicron lipoprotein particles. It can also be linked to mutations in genes which encode other proteins that are necessary for proper LPL function. This leads to an increase in triglyceride levels18,19. Patients with FCS often experience acute pancreatitis (AP) episodes, fatty deposits on the skin (eruptive xanthomas), abdominal pain, fatigue, impaired cognition, and enlargement of the liver or spleen. FCS is extremely rare, occurring in about one in one million people20,21. Until recently, there were no approved therapies for FCS, and most patients attempt to manage the condition through an extremely restrictive diet18,22. A novel treatment called volanesorsen has recently been authorized for use in the European Union23, and it has been shown to reduce triglyceride levels in phase II and III trials24,25. In the phase III trial, 77% of patients with FCS had triglycerides less than 750 mg/dL at three months of treatment25. As treatments are introduced, utilities are needed for economic modeling to examine their value.