Current management of hemophilia B: recommendations, complications and emerging issues

Abstract

Hemophilia B is a rare hereditary hemorrhagic disorder characterized by deficiency of the clotting factor IX (FIX). Hemophilia B patients experience mild-to-severe bleeding complications according to the degree of FIX defect. The mainstay of treatment of hemophilia B consists of replacement therapy and nowadays several plasma-derived and recombinant FIX products are commercially available. This article reviews the current management of hemophilia B patients analyzing the results of the most important clinical trials. In addition, it will focus on the more recent advances in the production of new FIX molecules aimed at the improvement of the clinical management of such patients.

Keywords::

• hemophilia B
• inhibitors
• long-acting FIX products
• plasma-derived FIX concentrates
• recombinant FIX products

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Replacement therapy with plasma-derived factor IX (FIX)or recombinant FIX products is the mainstay of the treatment of hemophilia B patients.

• Due to its better safety profile, recombinant FIX concentrate is nowadays the first choice of treatment in high-income countries.

• Primary prophylaxis is currently the best therapeutic approach to prevent joint damage in patients with severe hemophilia B.

• The development of inhibitory alloantibodies against FIX is a serious complication of replacement therapy that may be associated with severe allergic or anaphylactic reactions.

• Bypassing agents (rFVIIa and factor eight inhibitor bypassing activity) are both effective in the management of bleeding episodes in hemophilia B patients with inhibitors.

• Due to the low rate of success and the high risk of complications, immune tolerance induction is not routinely used in hemophilia B patients with inhibitors.

• The need for frequent FIX concentrate infusions due to the relatively short half-life of FIX is an important barrier to patients’ adherence to prophylactic regimens.

• Over the next 5 years, the availability on the market of new recombinant FIX molecules with prolonged half-life will improve the care of hemophilia B patients.