Background:
Homozygous familial hypercholesterolaemia (HoFH) is a rare and life-threatening genetic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels, important xanthomatosis and increased risk of premature atherosclerotic cardiovascular disease. Management of HoFH at an early stage is recommended but conventional lipid-lowering therapies (LLTs) dependent on the LDL-receptor for clearance of LDL particles, are usually not sufficient. However, agents acting independently of the LDL-receptor, such as inhibitors of microsomal triglyceride transfer protein (MTP) or angiopoietin-like protein 3 (ANGPTL3), administered in combination, on top of standard-of-care LLT constitute a promising therapy for HoFH.
Case summary:
The present case describes a long-term (>10 years) follow-up of a 52-year-old woman with severe HoFH, who was treated with conventional lipid-lowering medications (i.e. statins and ezetimibe) for several years before experiencing the risks and benefits that were encountered with the use of LDL-receptor-independent agents (MTP and ANGPTL3 inhibitors). This combination therapy demonstrated a good long-term safety and efficacy profile, while continuous monitoring of hepatic enzymes (sometimes requiring dose adjustments) and fat accumulation is recommended when using lomitapide.
Discussion:
Treating this HoFH patient with an LLT involving the combination of MTP and ANGPTL3 LDL-receptor-independent inhibitors (lomitapide and evinacumab, respectively) showed remarkable improvement in LDL-C levels, disappearance of xanthomatosis and regression in atherosclerotic plaques. In addition to safety and efficacy, one should question the affordability and access hurdle that emerging combination of expensive therapies might constitute in the future for the payers. These challenges could eventually limit the clinical use of those innovative treatments despite their clinical benefit.