Off-label evolocumab therapy achieved a greater than 90% reduction in triglyceride levels (nadir 118 mg/dL) in a patient with multifactorial chylomicronemia syndrome and a rare APOA5 variant.
Case Report (n=1)
No
Does off-label evolocumab reduce triglyceride levels in a patient with multifactorial chylomicronemia syndrome and a heterozygous APOA5 variant?
Off-label use of a PCSK9 inhibitor may provide significant adjunctive triglyceride-lowering benefits in patients with severe refractory hypertriglyceridemia and genetic susceptibility (APOA5 variant).
Effect estimate: >90% reduction
Absolute Event Rate: 118% vs 2170%
Severe hypertriglyceridemia (triglycerides ≥ 500 mg/dL) carries a high risk of recurrent acute pancreatitis and cardiovascular disease. Pathogenic variants in the APOA5 gene are associated with hyperlipoproteinemia type V and familial hypertriglyceridemia; however, detailed case reports involving variants of uncertain significance (VUS) with a severe clinical phenotype and documented therapeutic response are rarely published. A 46-year-old woman from rural Supía, Caldas, Colombia, presented with persistent very severe hypertriglyceridemia (peak: 2, 170 mg/dL), three hospitalizations for acute pancreatitis, and inadequate response to statins and fibrates. Targeted exome sequencing identified a heterozygous APOA5 VUS: c. 694T>C, p. Ser232Pro (NM₀52968. 5), classified as PM2/PP3 per ACMG criteria (ClinVar: VCV002617654. 3). An off-label PCSK9 inhibitor regimen achieved a greater than 90% triglyceride reduction (nadir: 118 mg/dL), though adherence has been intermittent due to economic and healthcare access barriers. This case highlights the diagnostic value of targeted genetic testing in severe familial hypertriglyceridemia and illustrates how an APOA5 VUS may underlie a severe multifactorial chylomicronemia phenotype. Segregation analysis and functional studies in first-degree relatives are warranted to support variant reclassification. This report also underscores the impact of healthcare access barriers on rare metabolic disease outcomes in rural Latin America.
Rios et al. (Mon,) conducted a case report in Multifactorial Chylomicronemia Syndrome (n=1). Evolocumab (PCSK9 inhibitor) vs. Baseline (prior statins and fibrates) was evaluated on Triglyceride levels (>90% reduction). Off-label evolocumab therapy achieved a greater than 90% reduction in triglyceride levels (nadir 118 mg/dL) in a patient with multifactorial chylomicronemia syndrome and a rare APOA5 variant.
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