Emicizumab: A Promising Option for Hemostatic Control in Acquired Hemophilia A

Acquired hemophilia A (AHA) is caused by development of autoantibodies or inhibitors against coagulation factor VIII, resulting in life-threatening bleeding diathesis. Hemostatic therapy with factor VIII bypassing agents is critical until inhibitors are eradicated; however, breakthrough bleeding and thromboembolic complications continue to be major problems. Immunosuppressive therapy (IST) remains the primary therapeutic option for inhibitor eradication. Emicizumab is a bispecific monoclonal antibody that mimics the function of activated factor VIII and achieves hemostasis even in the presence of inhibitors; it is approved for the treatment of congenital hemophilia A with and without inhibitors.

In an industry-funded, open-label, single-arm, phase 2 trial, investigators evaluated the efficacy of emicizumab alone in preventing bleeds in patients with newly diagnosed AHA. Patients received emicizumab for 12 weeks (loading dose of 6 mg/kg on day 1 and 3 mg/kg on day 2, followed by 1.5 mg/kg/week starting on day 8), with IST started after week 12.

Of 47 patients enrolled, median age was 76 years, median factor VIII activity was 1.4 IU/dL, and median inhibitor concentration was 11.4 BU/mL. During the intervention period, the mean bleeding rate per patient-week was 0.04, which was significantly lower than the predefined efficacy criterion of 0.15. No venous thromboembolic events were reported, but there were two ischemic strokes, unrelated to emicizumab. Among 33 patients who were on bypassing therapy, 18 discontinued it within 1 week of starting emicizumab. At week 13, median factor VIII activity remained low at 0.6 IU/dL; only 1 patient had spontaneous remission. Mortality was 9%: fatal bleeding in 2 patients, COVID-19 in 1, and cardiac arrest in 1.