A Multi-institution Prospective Assessment of Bone Health in Patients With Severe Hemophilia A on Factor VIII vs Factor Mimetic Prophylaxis (Efa Emi Bone Health Study)

Impaired bone health significantly contributes to morbidity and healthcare burden, particularly in patients with bleeding disorders. Identifying and addressing bone health issues early can reduce fracture rates, enhance quality of life, and minimize healthcare utilization. Although previous studies have demonstrated poor bone health in patients with severe hemophilia, limited data exist on the comparative effects of newer therapies, such as emicizumab and efanesoctocog alfa, on bone outcomes.

This study seeks to address this knowledge gap by prospectively investigating bone mineral density in patients with severe hemophilia A on these two prophylactic therapies. Additionally, the study will examine markers of bone remodeling, thrombin generation, and joint health. Insights gained will provide critical information on whether factor-based therapies confer superior bone health benefits compared to non-factor therapies.

In summary, the thrombin/PAR1 axis plays a crucial role in regulating the dynamic structure of bone. Patients with severe Hemophilia A experience decreased thrombin generation, which is hypothesized to contribute to reduced bone formation and increased bone resorption. Given that Efanesoctocog alfa maintains higher factor VIII levels compared to Emicizumab, leading to better thrombin generation, we hypothesize that Efanesoctocog alfa will result in greater improvements in bone mineral density (BMD) in persons with Hemophilia A (PwH) compared to Emicizumab that would prevent future fractures.