The effect of volanesorsen treatment on the burden associated with familial chylomicronemia syndrome: the results of the ReFOCUS study

<p><b>Background</b>: Volanesorsen, an investigational inhibitor of apoC-III synthesis, significantly reduced triglyceride levels in clinical trials in patients with familial chylomicronemia syndrome (FCS), a rare genetic disorder characterized by marked chylomicronemia leading to a spectrum of symptoms, including recurrent abdominal pain and episodes of potentially fatal acute pancreatitis (AP).</p> <p><b>Objective</b>: To determine the effect of volanesorsen on burden of disease on patients with FCS</p> <p><b>Methods</b>: ReFOCUS was a retrospective global web-based survey open to patients with FCS who received volanesorsen for ≥3 months in an open-label extension study. The survey included questions about patients’ experiences before and after volanesorsen treatment.</p> <p><b>Results</b>: Twenty-two respondents had received volanesorsen for a median of 222 days. Volanesorsen significantly reduced the number of symptoms per patient across physical, emotional, and cognitive domains. Significant reductions from baseline were reported for steatorrhea, pancreatic pain, and constant worry about an attack of pain/AP. Respondents reported that volanesorsen improved overall management of symptoms and reduced interference of FCS with work/school responsibilities. Reductions in the negative impact of FCS on personal, social, and professional life were also reported.</p> <p><b>Conclusions</b>: Treatment with volanesorsen has the potential to reduce disease burden in patients with FCS through modulation of multiple symptom domains.</p

Clinical characteristics and laboratory parameters of children with and without atherogenic dyslipidemia.

<p>BMI, body mass index; BP, blood pressure; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; ApoB, apolipoprotein B; ApoAI, apolipoprotein AI; hs-CRP, high sensitivity C Reactive Protein; HOMA-IR, homeostasis model assessment of IR index.</p><p>hs-CRP and adiponectin values are reported as median (interquartile range)</p><p>* p<0.05;</p><p>** p<0.01;</p><p>*** p<0.001</p><p>Clinical characteristics and laboratory parameters of children with and without atherogenic dyslipidemia.</p

Flow diagram for classification of children with atherogenic dyslipidemia.

<p>Flow diagram for classification of children with atherogenic dyslipidemia.</p

Prevalence in the cohort of probands with atherogenic dyslipidemia of non-synonymous exonic variants in the LPL gene.

<p>^<b>a</b>The name at protein level is without the pro-peptide.</p><p>n = number of variant alleles / number of total alleles</p><p>^<b>b</b>Frequency from database 1000 genomes EUR;</p><p>^<b>c</b>Frequency from ESP6500:European_American, the only available for L365V SNP.</p><p>Depending on the sample size and absolute frequencies in the contingency table:</p><p>^<b>d</b>Fisher exact test or</p><p>^<b>e</b>χ² was applied.</p><p>^# = annotations for the new variant are: NC_000008.11:g.19948306G>A; NG_008855.1:g.14236G>A; NM_000237.2:c.215G>A; NP_000228.1:p.Ser45Asn</p><p>* = statistically significant at indicated P level.</p><p>Prevalence in the cohort of probands with atherogenic dyslipidemia of non-synonymous exonic variants in the LPL gene.</p

Clinical characteristics and laboratory parameters of parents and siblings of children with and without atherogenic dyslipidemia.

<p>BMI, body mass index; BP, blood pressure; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; ApoB, apolipoprotein B; ApoAI, apolipoprotein AI; hs-CRP, high sensitivity C Reactive Protein; HOMA-IR, homeostasis model assessment of IR index. hs-CRP and adiponectin values are reported as median (interquartile range)</p><p>* P<0.05;</p><p>** p<0.01;</p><p>*** p<0.001 between parents</p><p>^{<b>‡‡</b>} p<0.01;</p><p>^{<b>‡‡‡</b>} p<0.001 between siblings</p><p>Clinical characteristics and laboratory parameters of parents and siblings of children with and without atherogenic dyslipidemia.</p