Changing paradigm of prophylaxis with longer acting factor concentrates

Abstract

Beginning in the 1960s the care of persons with haemophilia began to improve dramatically through a series of transformative improvements in care: development of lyophilized factor concentrates, home care programmes, prophylaxis and (due to the tragedy of HIV/hepatitis) the development of virally safer plasma-derived and recombinant factor concentrates. Prophylaxis, if commenced early and given in sufficient dose/frequency has been shown to allow persons with haemophilia to maintain excellent joints and lead normal lives. Yet the relatively short half-lives of factor (F) VIII and IX concentrates leads to the need for frequent venous access. This remains a significant burden for patients with haemophilia on prophylaxis causing in many cases reduced patient adherence to prophylaxis and negative longterm outcomes. The last 5 years have witnessed a flourish of new bioengineered longer acting FVIII and IX concentrates manufactured using different technologies (pegylation or fusion to Fc/albumin). These products (especially the longer acting FIX concentrates) are likely to have profound implications on prophylaxis. With these longer acting factor concentrates prophylaxis regimens will almost certainly change. This will involve changes in what trough levels are targeted and how frequently factor is administered. It is hoped that these changes may improve patients' adherence to prophylaxis and their quality of life. These long-acting factor concentrates will undoubtedly have cost repercussions and will raise important questions regarding how decisions about choosing one longer acting concentrate over another, and whether these products are interchangeable, are made. This article will review what changes may ensue with the advent of these new longer acting factor concentrates.

Keywords: Fc or albumin fusion technology; haemophilia; longer acting factor concentrates; pegylation; prophylaxis.