Is it time to move beyond the 1% target?
In haemophilia A, prophylaxis aims to increase trough levels of factor VIII above 1% through regular, long term intravenous administration of concentrates, with the ultimate aim of converting a severe bleeding phenotype to a moderate phenotype. In a Bayer-sponsored symposium on prophylaxis at the ISTH meeting in Amsterdam, Professor Cedric Hermans from Louvain, Belgium, noted that despite several decades of research and clinical experience, the optimal prophylactic approach was still a matter of debate and “it has never been clearly verified whether the goal of converting severe to moderate disease has been fully achieved.”
He said that clinicians frequently targeted levels above 1% for those severe patients with target joints, those who present with repeated breakthrough bleeding, those treated with antithrombotic agents, and prior to undertaking physical activity.
He argued that because of its low prevalence compared with severe haemophilia, the clinical outcomes of patients with moderate haemophilia have been poorly investigated. But studies had shown that the bleeding frequency in moderate haemophilia patients with a residual factor VIII level of 3-5% was much lower than in those with a residual factor VIII level of 1-2%.
He proposed that the goal of prophylaxis, at least in those patients with severe haemophilia characterized by a severe bleeding phenotype, should be to achieve a mild form of the disease, aiming for factor VIII levels above 5%, which he said “would provide better protection against subclinical bleeds and would preserve the joint status.”
Of course, using currently available short-acting concentrates this would require more frequent infusions, perfect adherence and good venous access. “My assumption is that the longer acting products currently being developed could offer new opportunities to obtain higher trough levels,” said Professor Hermans. We are always thinking about the new products being given to patients at a lower frequency. But you could decide to give the longer acting products at the same frequency in order to target higher trough levels.”
The acceptability of such a change in treatment strategy is likely to depend on how the new concentrates are priced and on the cost-effectiveness arguments deployed. Commissioners will no doubt be watching with interest as this debate unfolds. What’s your view? Log in to Haemnet and tell us what you think.