Effects of Emicizumab vs. Factor VIII Prophylaxis on Joint and Bone Health in Severe Hemophilia A

Summary: This retrospective/prospective, non-randomized controlled study, whereby patients will be included in 1 of 2 groups depending on their current treatments as outlined below. Patients will be assigned to a specific group by the clinician/PI based on their current regimen with the intent to stay on this regimen for the next 3 years.

Duration of Study and Subject Participation: Study subject enrollment is anticipated to occur over about 12 months and study duration per subject will be 3 years. Thus a total study duration of 4 years is anticipated.

Intervention: By using musculoskeletal ultrasound, the investigators will measure joint health among participants and assess joint health changes over 3 years compared between group A (factor prophylaxis) vs. group B (emicizumab prophylaxis) as assessed by MSKUS at baseline and after 3 years. Other outcomes such as bone density, comparative assessment of joint and overall health status, and exploration of potential biomarkers for joint and bone health will also be assessed.

Inclusion criteria

• Male gender
• Severe hemophilia A (factor VIII < 1%)
• Age ≥ 16 year
• Either on prophylaxis with factor VIII or emicizumab with the intention to stay on the current regimen for the next 3 years
• Willing and able to give written informed consent/assent
• Willing to undergo MSKUS, DEXA scan +/- collection of blood sampling for repository biomarkers
• Willing to come in for baseline and 3 yearly visits
• Willing to answer phone survey for bleeding and safety every 3 months

Exclusion criteria

• Current FVIII inhibitor of > 0.6 BU
• Unable to take FVIII replacement
• Other known bleeding disorder
• Other rheumatologic disorder affecting joints
• Other known neuromotor defect (making physical exam difficult)