Evinacumab and reduced lipoprotein apheresis in pediatric homozygous familial hypercholesterolemia: a retrospective study on LDL-C.

BACKGROUND AND AIMS: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) from birth, leading to accelerated atherosclerotic cardiovascular disease and premature death if untreated. Evinacumab, a monoclonal antibody targeting angiopoietin-like 3 (ANGPTL3), offers an LDL receptor-independent pathway to lower LDL-C. This study aimed to evaluate the effect of evinacumab on lipid levels and its potential to reduce lipoprotein apheresis (LA) frequency in children and adolescents with HoFH.

METHODS

This was a single-center, retrospective, observational study of six patients aged 10-19 years who had genetically confirmed HoFH and were treated with stable doses of lipid-lowering therapy (LLT) and evinacumab with or without LA at the Medical University of Vienna. Demographic characteristics, lipid levels, and treatment details were collected.

RESULTS

At the first visit, LDL-C levels ranged from 521 to 870 mg/dL (13.5-22.5 mmol/L). With stable LLT plus LA, pre-LA LDL-C levels were reduced to 212-352 mg/dL (5.5-9.1 mmol/L) and, after evinacumab was added, further reductions to 90-201 mg/dL (2.3-5.2 mmol/L) were observed. However, during periods of reduced LA frequency, pre-LA LDL-C levels increased to 105-216 mg/dL (2.7-5.6 mmol/L), exceeding the target of 115 mg/dL (3.0 mmol/L) in three out of four patients. LA frequency reduction from weekly to three times per month was only possible in one patient, but no patients had termination of LA.

CONCLUSIONS

Evinacumab effectively lowers LDL-C in children and adolescents with HoFH. However, its ability to facilitate long-term reduction in LA frequency was not shown and remains unclear.