The development of neutralizing antibodies, also called inhibitors, is a major complication of hemophilia treatment in children. Although factor replacement therapies are effective in restoring functional coagulation, the presence of inhibitors often leads to significant morbidity and lower quality of life. The clinical management of children with inhibitors has recently evolved with the availability of novel therapies.
In a review article published in the British Journal of Haematology, Guy Young, MD, of the Hemostasis and Thrombosis Center and Clinical Coagulation Laboratory at the University of Southern California in Los Angeles, summarized current treatment strategies for children with hemophilia and inhibitors and provided recommendations to help guide clinical practice.
“There exists a substantial unmet need for children with inhibitors, and though novel approaches to completely prevent or eradicate inhibitors would indeed be welcome, at present, there are no such therapies in clinical development,” Dr Young wrote.
Treatment Options for Children With Inhibitors
Historically, certain forms of hemophilia were often considered fatal because of the reoccurrence of life-threatening bleeding episodes. Today, the prognosis of hemophilia has substantially improved due to access to effective treatment options, such as clotting factor concentrates. These therapies are usually administered on a prophylactic basis, with dosing and frequency varying based on the specific type of hemophilia.
In general, clotting factor concentrate therapy is safe and effective for patients with various forms of hemophilia. However, some patients may develop inhibitors while on treatment, which can neutralize the effects of factor replacement therapy. The estimated risk of inhibitor formation is approximately 30% in patients with severe hemophilia A and approximately 2% in hemophilia B, but estimates vary depending on the study. Patient-specific risk factors for inhibitor development include race, specific immune markers, family history, and hemophilia genotype.
“The management of inhibitors in patients revolves around two basic principles: eradication of the inhibitor and management of bleeding,” Dr Young explained. “I believe that achieving inhibitor eradication remains the most important goal, although there are opinions to the contrary following the licensure of emicizumab.”