Physicians' Academy for Cardiovascular Education

Longer-term treatment with PCSK9 antibody safely lowers LDL-c in HoFH patients

Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study

Raal FJ, Hovingh GK, Blom D, et al., - Lancet Diabetes Endocrinol. 2017 Feb 16. doi: 10.1016/S2213-8587(17)30044-X


Untreated patients with homozygous familial hypercholesterolaemia (HoFH) have substantially reduced clearance of plasma LDL cholesterol, and consequently typically their LDL-c concentrations can be greater than 13 mmol/L. A reduction of almost 90% is needed to reach the goal of <1.8 mmol/L, recommended for those with very high CVD risk [1,2].

In addition to modestly effective conventional therapy such as statins and ezetimibe, LDL apheresis can be used, when available. Inhibitors of apolipoprotein B synthesis (mipomersen) and microsomal triglyceride transfer protein (lomitapide) can yield additional LDL-c lowering, but their use is hampered by substantial side-effects, high costs and poor long-term adherence [3-5]. Moreover, even with these drugs, LDL-c concentrations in HoFH patients remain far from optimal, and apheresis is still frequently required.

The PCSK9-directed antibody evolocumab (given 420 mg monthly) has been shown to reduce LDL-c by 31% compared with placebo, in HoFH patients [6]. This is an interim analysis of the ongoing open-label TAUSSIG study evaluating the long-term safety and efficacy of evolocumab in a subset of study participants with HoFH (n=106, 105 with genetic diagnosis) receiving evolocumab, with (n=34) or without apheresis (n=72). The TAUSSIG study will follow patients for 5 years, but in the current analysis, patients received a minimum of 12 weeks, and mean study exposure was 1.7 years (SD: 0.63). Patients received evolocumab 420 mg every month, or every 2 weeks if on apheresis, immediately after apheresis. After 12 weeks, in those not on apheresis, the dose could be increased to 420 mg every 2 weeks at the investigators’ discretion.

Main results

LDL-c reductions in those on apheresis at week 12 and 48 did not significantly differ from reductions achieved in those only receiving drug therapy.


This interim analysis represents the largest and longest study of lipid-lowering medication in HoFH patients to date, the results of which support the long-term tolerability and safety of the PCSK9 antibody evolocumab. 95% of patients were still in the study at 48 weeks. Evolocumab substantially reduced LDL-c concentrations in HoFH patients on standard lipid-lowering therapy, with or without apheresis.

The study also describes treatment of adolescent patients, who showed a decreased treatment response, but numbers were low.


Show references

Find this article online at Lancet Diabetes Endocrinol.