Factor VIII therapy for hemophilia A: current and future issues

Abstract

Hemophilia A is a congenital, recessive, X-linked bleeding disorder that is managed with infusions of plasma-derived or recombinant factor (F) VIII. The primary considerations in FVIII replacement therapy today are the: 1) immunogenicity of FVIII concentrates, 2) role of longer-acting FVIII products, 3) prophylactic use of FVIII in children and adults with severe hemophilia A, and 4) affordability and availability of FVIII products. Improving patient outcomes by increasing the use of FVIII prophylaxis, preventing or eliminating FVIII inhibitors, and expanding access to FVIII concentrates in developing countries are the major challenges confronting clinicians who care for patients with hemophilia A.

Keywords::

• factor concentrate
• FVIII
• gene therapy
• genetics
• hemophilia A
• immunogenicity
• longer-acting FVIII
• prophylaxis

Financial & competing interests disclosure

None of the authors received payment for participating in the preparation of this manuscript.

LA is on the data safety monitoring boards of Baxter and Octapharma. RL has received consultancy fees and honorarium from Baxter, Bayer, Novo Nordisk and Octapharma during the last 5 years. KM has received consultancy fees from Alnylam, Baxter, Bayer and CSL Behring and serves as chairman of the board of Hematologic Technologies. SP has received consultancy fees from Baxter, Biogen Idec, CSL Behring, Novo Nordisk and Pfizer. Michele Grygotis, an independent consultant, provided medical writing services that were funded by Baxter Healthcare Corporation. The authors have no other 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 apart from those disclosed.

Key issues

• Hemophilia A is a congenital, recessive, X-linked bleeding disorder that is treated with infusions of plasma derived or recombinant factor (F) VIII.

• The primary considerations in FVIII replacement therapy are the

  • – Immunogenicity of FVIII concentrates.

  • – Role of longer-acting FVIII products.

  • – Prophylactic use of FVIII in children and adults with severe hemophilia A.

  • – Affordability and availability of FVIII products.

• Improving patient outcomes by increasing the use of FVIII prophylaxis, preventing or eliminating FVIII inhibitors and expanding access to FVIII concentrates in developing countries are the major challenges in hemophilia care today.

Notes

* Risk factors for ITI failure: peak inhibitor titer >200 BU; titer at ITI start >10 BU, age >7 years, time between inhibitor development and start of ITI >2 years.

** Continuous is defined as the intent of treating 52 weeks/year and at least 45 weeks/year (85%).

† Large joints – ankles, knees, hips, elbows and shoulders.