116 - Differential response to PCSK-9 inhibitor therapy is related to the type of low density lipoprotein receptor gene mutation in patients with homozygous Familial Hypercholesterolaemia (ID 1340)
Abstract
Background and Aims
PCSK9 inhibitors (PCSK9i) are now recognised as an effective way to treat homozygous familial hypercholesterolaemia (HoFH) FH. The objective is to report the response of two HoFH cases towards PCSK9i therapy.
Methods
We administered PCSK9i, alirocumab 75 mg once every 2 weeks for almost 1 year to two cases of HoFH. Case 1 is a 30-year-old Malay lady who carries a well-documented pathogenic LDLR c.1187-2A>G variant, leading to skipping of the entire exon 3 and inclusion of intron 3 during mRNA splicing, resulting in the production of a non-functional LDL receptor. Case 2 is a 24-year-old Malay man who inherits a novel LDLR c.2553_2556delGATGinsTCT deletion at axon 18 located at LDLR cytoplasmic tail domain. They were given rosuvastatin 40 mg and ezetimibe 10 mg throughout the course of PCSK9i treatment.
Results
In Case 1, LDL-C level showed insignificant reduction, ranging from 15.8-19.6 mmol/L, from a baseline of 18.6mmol/L, while on PCSK9i therapy. After stopping the alirocumob, the LDL-C level remained high at 15.0 mmol/L. In contrast, Case 2 showed significant LDL-c reduction of 72% (12.5mmol/L to 3.5mmol/L) compared to his baseline. Furthermore, his LDL-C levels remained low, and did not elevate to baseline level prior to treatment, for at least up to 12months after alirocumab withdrawal.
Conclusions
HoFH patients exhibit different LDL-c response to PCSK9i therapy, depending on the location of affected LDLR allele and protein. Further studies are required to address HoFH patients who may benefit maximally from PCSK-9 inhibitor.
