Current treatment of hemophilia
Hemophilia A and B are bleeding disorders in which patients bleed abnormally from trivial causes. Prior to modern treatment, patients suffered from recurrent abnormal bleeding leading to crippling, painful, arthropathies and premature death. Starting in the 1960’s and 70’s, factor replacement became available and was given in the home.3,4 Bleeding episodes could finally be controlled. Patients underwent elective surgeries. However, joint disease and other complications persisted. Life expectancy improved but remained far from normal. Factor replacement led to alloimmunization (inhibitor) in some patients, which complicated treatment immensely. In the 1980s contamination of factor concentrates with HIV and hepatitis C devastated the hemophilia community.3,4 In this environment, alternatives to episodic plasma derived factor replacement, including gene therapy, were proposed.5Fortunately, advances in treatments in the 1990s started to turn the tide on the complications of hemophilia. Recombinant factor products were developed and improvements in plasma derived products eliminated the risk of HIV and hepatitis C transmission.4Prophylactic infusion of factor reduced joint bleeding and other complications.6 Life expectancy improved further. However, the burden of treatment was significant. Prophylactic regimens required intravenous infusions at least twice weekly, and daily to achieve immune tolerance for those alloimmunized.6,7To facilitate the infusion, indwelling catheters were used. This led to infectious and thrombotic complications.8 The 2010s saw further improvements in treatment. Extended half-life products were developed that reduced the burden of prophylactic treatment.9,10 Patients with hemophilia A and B are now treated with prophylactic regimens with once weekly (or less) infusions.9,11 The factor VIII mimetic Emicizumab has revolutionized the treatment for hemophilia A.12-14The annualized bleeding rate (ABR) for people with hemophilia A (alloimmunized or not) is approaching zero with subcutaneous injections of Emicizumab.12-14 This can be given as infrequently as once monthly.13,14 The life expectancy of people with hemophilia is now approaching normal.15Additional improvements in treatments are on the horizon. Treatments aimed at rebalancing hemostasis are nearing regulatory approval.14, 16,17 Thus, a subcutaneous treatment for hemophilia B (alloimmunized or not) may soon be available. In diseases other than hemophilia, extended half-life strategies for monoclonal antibodies have been developed with therapeutic levels lasting 6 months.18 Similar technologies could be applied to hemophilia treatments, reducing the need for subcutaneous injections to 2-3 times a year.