Differential effects of volanesorsen on apoC-III, triglycerides and pancreatitis in familial chylomicronemia syndrome diagnosed by genetic or non-genetic criteria.

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Sotirios Tsimikas, Henry N Ginsberg, Veronica J Alexander, Ewa Karwatowska-Prokopczuk, Andy Dibble, Lu Li, Joseph L Witztum, Robert A Hegele
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引用次数: 0

Abstract

Background: Familial chylomicronemia syndrome (FCS) is diagnosed by genetic or non-genetic criteria.

Objective: To assess responses to treatment of apolipoprotein (apo)C-III, triglycerides, and pancreatitis events in patients with FCS-based diagnostic methods.

Methods: APPROACH enrolled 66 patients with FCS randomized to volanesorsen or placebo for 12 months. In 50 participants, genetic confirmation of FCS was based on the presence of pathogenic bi-allelic variants in LPL, APOC2, APOA5, GPIHBP1, or LMF1 genes. In 16 participants without a genetic diagnosis, FCS was diagnosed using clinical criteria and post-heparin lipoprotein lipase activity ≤20 % of normal. Plasma levels of apoC-III, triglycerides and related variables were measured at 3, 6 and 12 months.

Results: No significant differences were present in mean apoC-III reductions with volanesorsen at 3, 6 or 12 months in patients with FCS diagnosed either genetically or non-genetically. In contrast, the triglyceride reductions were statistically less robust in patients with genetic diagnosis at each timepoint, with mean (95 % confidence interval) percent reduction in triglycerides of -68.7 % (-78.7, -58.6) vs. -84.0 % (-99.4, -68.6), p = 0.014 at Month 3; -58.2 % (-78.1, -38.2) vs. -84.5 % (-122.4, -46.7), p = 0.009 at Month 6; and -35.6 % (-57.7, -13.4) vs. -69.0 % (-105.0, -33.1), p = 0.005 at Month 12. Patients with a genetic diagnosis had significantly lower response rates for achieved triglycerides <500 mg/dL, <750 mg/dL, <880 mg/dL and <1000 mg/dL than patients with a non-genetic diagnosis. All 5 episodes of acute pancreatitis occurred in patients with a genetic diagnosis.

Conclusions: For a similar reduction in apoC-III in response to volanesorsen, triglyceride reduction is attenuated in patients with genetically versus non-genetically diagnosed FCS.

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来源期刊
CiteScore
7.00
自引率
6.80%
发文量
209
审稿时长
49 days
期刊介绍: Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner. Sections of Journal of clinical lipidology will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.
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