Prophylaxis for Hemophilia A with Inhibitors

Antibody formation renders factor VIII replacement therapy ineffective in up to 30% of patients with hemophilia. Preliminary studies have shown that emicizumab — a recombinant bispecific monoclonal antibody that bypasses the requirement for factor VIII — decreased the frequency of bleeding in severe hemophiliacs (NEJM JW Oncol Hematol July 2016 and N Engl J Med 2016; 374:2044).

To further evaluate emicizumab in this setting, investigators have conducted an industry-sponsored, phase III, multicenter, open-label randomized trial in 109 men with hemophilia A with a history of high titer factor VIII inhibitors. Patients received either no prophylaxis or prophylaxis with emicizumab (3 mg per kg subcutaneously weekly for 4 weeks, followed by 1.5 mg/kg weekly for 20 weeks). Breakthrough bleeding during the trial was managed with either activated prothrombin complex concentrate or recombinant factor VIIa.

The annualized bleeding rate was lower with emicizumab than without (2.9 vs. 23.3 events; P<0.001), and 63% of patients receiving the drug had no bleeding. The bleeding rate with emicizumab was significantly lower than with previous bypassing-agent prophylaxis (3.3 vs. 15.7 events; P<0.001) or with episodic treatment (1.7 vs. 21.6 events; P <0.001). Health-related quality-of-life scales also favored emicizumab. Injection site reactions were the most frequently reported adverse effect of the drug, but thrombotic events occurred in five emicizumab-treated patients who were given activated prothrombin complex concentrate for breakthrough bleeding.