Monoclonal antibodies for the treatment of high cholesterol

This paper studied the use of the drugs evolocumab and alirocumab in reducing cholesterol levels in the body. The authors concluded that PCSK9 monoclonal antibodies will be important in treating hypercholesterolemia.

Low-density lipoprotein (LDL) is a type of fat present in the blood. LDL binds to and carries cholesterol in the blood. Too much LDL is harmful to the body. Hypercholesterolemia refers to a high level of low-density lipoprotein (LDL). Familial hypercholesterolemia is a genetic condition causing high levels of LDL. In familiar hypercholesterolemia, various mutations in the low-density lipoprotein receptor (LDLR) gene prevent LDL binding to the LDL receptor, therefore preventing cholesterol in the blood from being broken down.

PCSK9 monoclonal antibodies are a group of drugs that work to lower cholesterol levels. They work by allowing LDL to be removed from the body. Evolocumab (Repatha) and Alirocumab (Praluent) are two types of PCSK9 monoclonal antibodies which have recently been approved for the treatment hypercholesterolemia. 

This study aimed to summarise results from trials which analyzed the safety and effectiviness of evolocumab and alirocumab.

A study of 24 trials found that patients receiving PCSK9 monoclonal antibodies had a 48% reduction in LDL levels compared to patients who did not receive the drug.

One study showed that LDL decreased from 122.8 to 48.3 mg/dL in patients who received alirocumab. These patients also had a lower occurrence of death from heart disease, heart attack, stroke, and chest pain. With regards to adverse events (undesired effect of treatment), muscle pain was more likely to occur.

One study found that in patients with familial hypercholesterolemia, LDL was reduced by 79.0 mg/dL with PCSK9 monoclonal antibodies. However, a patient with a genetic mutation which causes no LDL receptor to be produced did not respond to evolocumab and LDL concentrations increased over 12 weeks.

Another study found that patients had a 51% lower risk of having a heart attack when treated with a PCSK9 monoclonal antibody.

In another study, neither alirocumab nor evolocumab significantly affected the occurrence of adverse events, compared to patients who did not receive the drug.

One study found that patients who received alirocumab were 1.48 times more at risk of injection site reactions compared to patients who did not receive alirocumab.  On the other hand, the risk was similar for patients who received evolocumab.

The authors concluded that PCSK9 monoclonal antibodies will be important in treating hypercholesterolemia, especially in patients needing large LDL reductions.

Consult your physician regarding the risks and benefits of evolocumab and alirocumab.