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.