Emicizumab in Previously Untreated Patients and Minimally Treated Patients With Hemophilia A: A Comparative Study Between Two International Cohorts.

Abstract

Background: Hemophilia A (HA) is a rare bleeding disorder caused by coagulation factor VIII (FVIII) deficiency. Prophylactic FVIII replacement therapy is essential for preventing bleeds, but it carries a risk of inhibitor development, especially in previously untreated and minimally treated patients (PUPs and MTPs, respectively). Emicizumab, a bispecific monoclonal antibody that mimics FVIII function, offers a promising alternative for HA prophylaxis due to its subcutaneous administration and favorable safety profile.

Methods: This study evaluated the real-world safety and efficacy of emicizumab prophylaxis in two international hemophilia treatment centers (HTC). The first HTC included a cohort of 22 MTPs with severe HA (FVIII <1%) and fewer than five prior FVIII exposure days, while the second HTC enrolled 19 PUPs with severe HA.

Results: The median age at emicizumab prophylaxis initiation was 5 months for the MTPs and 8 months for the PUPs. Patients were followed for a median of 27 and 29 months, respectively. The median time to first bleed was 13 months for MTPs, with a significantly longer time to first bleed noted in the PUPs cohort. Safety outcomes were favorable, with neither intracranial hemorrhage nor anti-emicizumab antibodies reported. Four patients, 18% of all MTPs, developed FVIII inhibitors, all associated with high-risk genetic mutations and prior bleeding events.

Conclusions: Our findings support the early use of emicizumab as a safe and effective prophylactic strategy in infants with severe HA. However, the observed inhibitor rate underscores the need for ongoing monitoring and research to optimize care, particularly in vulnerable populations.