Concomitant Use of rFVIIa and Emicizumab in People with Hemophilia A with Inhibitors: Current Perspectives and Emerging Clinical Evidence

Emicizumab, a humanized, bi-specific, monoclonal antibody subcutaneously administered, mimicking the function of FVIIIa, represents a milestone in treatment of patients affected by hemophilia A complicated with inhibitors. The HAVEN 1 and 2 studies have clearly established its superiority compared to bypassing agents for routine prophylaxis in preventing or reducing bleeding episodes in adult and pediatric patients with inhibitors. However, its protection against bleeding is only partial, and concomitant use of a bypassing agent may be required with potential prothrombotic risk. The emicizumab Phase III trials (HAVEN 1, 2 and 4) have shown that the traditional bypassing agents, activated prothrombin complex concentrates or recombinant activated factor VII (rFVIIa), may be necessary for the treatment of breakthrough bleeds or surgery management. A post hoc analysis in particular has shown that the concomitant use of emicizumab and rFVIIa is safe and no thrombotic events have been described. The review describes the state of the art of the concomitant use of emicizumab and rFVIIa for treating acute bleeding and surgeries, its efficacy and safety and the lack of thrombotic events associated with this treatment modality. Data still derive mainly from HAVEN trials; however, the availability of emicizumab in clinical practice is progressively increasing the number of patients treated and no adverse events directly attributed to this agent have occurred. The availability of guidelines for the use and dosing of rFVIIa during emicizumab prophylaxis is useful in clinical practice for managing suspected or ongoing bleeding, emergency situations and elective invasive procedures. In the next years, careful prospective post-licensure surveillance to monitor safety of rFVIIa use during prophylaxis with emicizumab is highly recommended.