In some cases, hemophilia patients develop antibodies against the coagulation factors administered during therapy. These are then no longer effective in the further course. In order to remove such so-called inhibitors, a procedure called immunotolerance therapy has always been used. This, however, is expensive, painful and often has limited effectiveness.
Approximately 30% of factor VIII hemophilia patients (hemophilia A) and approximately 3% of patients with factor IX hemophilia (hemophilia B) develop inhibitory antibodies against coagulation factor replacement therapy over a period of 50 treatment days. Therefore, the primary treatment objective in these patients is to eradicate these inhibitors and induce an immunotolerance that allows further treatment of the patients.
However, immunotolerance therapy is coming under pressure from new drugs, such as emicizumab, and is being questioned more frequently today. The main criticisms of the opponents of immunotolerance therapy are the high costs, the necessity of a twice daily i.v. application, a high load during treatment, and the uncertain outcome. According to studies, the success rate of immunotolerance therapy is not more than 70%.
On the other hand, the proponents of the method praise the Bonn Protocol, which has long been used reliably. For 40 years, it has helped to reduce the inhibition bodies on average within four months. Relapse rates are also very low after successful immunotolerance development.
Emicizumab is a highly effective alternative treatment for hemophilia A, which significantly reduces bleeding rates and can even be used prophylactically. However, the drug does not lead to any change in the inhibition body level.
However, the freedom from inhibitors in the further life of the patient is often a basic prerequisite for safe handling during an operation or to be able to use the gene therapy that is still under development one day. The gene therapy for the treatment of hemophilia is currently in Phase-III of clinical approval, so we still have to wait for a little. However, early immunotolerance development is one of the prerequisites for providing patients affected by inhibitors with safe access to gene therapy in the future.
For patients with hemophilia B who develop inhibitors, immunotolerance therapy will probably continue to be important. This affects about 3% of people with hemophilia B who cannot be treated with emicizumab, which was developed for hemophilia A only. On the other hand, emicizumab provides patients with hemophilia A with an easier to administer and less painful therapy to reduce the tendency to bleed. However, this therapy option does not influence inhibitors.
Already today, real-world trends show that immunotolerance therapy is increasingly losing its influence in hemophilia A treatment. However, it will not disappear completely in hemophilia A, because there are still patients who benefit from immunotolerance therapy - this is the only way to eradicate inhibitors.
Source:
Satellite Symposium "Hemostaseological Challenges" (Organizer: CSL Behring GmbH), GTH19; Berlin, 28.02.2019