Contemporary Management of Familial and Multifactorial Chylomicronemia Syndromes in Italy: Insights From the National Lipigen Registry.

Background: We aimed to compare the molecular and clinical characteristics of patients identified in Italy as affected by either familial chylomicronemia syndrome (FCS) or multifactorial chylomicronemia syndrome (MCS) and to assess the overall benefit of novel triglyceride-lowering therapies prescribed to these patients within the routine clinical care.

Methods: From the national LIPIGEN-sHTG (Lipid Transport Disorders Italian Genetic Network-Severe Hypertriglyceridemia) registry, 169 patients (57 FCS, 51 MCS, 61 variant-negative, variant-negative MCS) were retrospectively analyzed. Data on clinical and genetic characteristics, medical history, and medications were collected. Peak triglyceride levels were used to define untreated lipid phenotypes.

Results: In FCS, 72% exhibited biallelic LPL and 28% non-LPL variants; in MCS, 38% (n=19) carried LPL variants, and 38% (n=19) carried APOA5 variants, whereas the remaining individuals were carriers of LMF1 (n=3), GPIHBP1 (n=2), and CREB3L3 or GPD1 variants (n=8), respectively. Peak TGs were highest in FCS (3000 mg/dL [interquartile range, 2116.0-4265.0]), followed by MCS (1817 mg/dL [interquartile range, 1370.0-3062.0]) and variant-negative MCS (1340.0 mg/dL [interquartile range, 946.5-2508.5]; P<0.001). FCS showed a 3.4-fold higher risk of acute pancreatitis than others, whereas no significant differences were observed between groups in the prevalence of atherosclerotic cardiovascular diseases. In the subset of patients with FCS receiving novel therapies (lomitapide or volanesorsen; 35%), triglyceride levels decreased by 62%, as compared with an 11% reduction in those on conventional treatment. Across the cohort, posttreatment triglyceride levels were 895 mg/dL in FCS, 352 mg/dL in MCS, and 386 mg/dL in variant-negative MCS.

Conclusions: As compared with MCS, patients with FCS showed a more severe phenotype and higher prevalence of LPL variants. Lomitapide and volanesorsen provide better triglyceride control, yet only one-third of FCS were treated with these drugs in the routine clinical practice.