Quantifying the optimal factor VIII levels to achieve patient-centric and clinician-relevant outcomes among people with hemophilia A: a SHELF elicitation study

Abstract

Background: Hemophilia A is an inherited bleeding disorder caused by a deficiency of clotting factor VIII (FVIII), leading to joint bleeding and arthropathy. While prophylactic FVIII therapy reduces bleeding, evidence suggests maintaining higher FVIII levels (FL) may better protect joint health, particularly in physically active individuals and those with joint damage. However, data on optimal FLs required to prevent joint deterioration and complications remains limited. Research design and methods: This study utilized the Sheffield Elicitation Framework (SHELF) methodology to elicit expert opinions on optimal FLs for patient-centric and clinical outcomes. Five European hemophilia experts participated in virtual workshops, providing probability-based estimates of FLs required to prevent bleed-related hospitalizations, orthopedic procedures, target joint incidence, and support physical activity without additional infusions or joint damage. Results: Experts consistently recommended higher FLs for individuals with joint damage than for those without. Optimal average FLs ranged from 24% to 51%, exceeding traditionally recommended prophylactic trough levels (3–5%). Considerable uncertainty was noted around FLs for physical activity, reflecting the complexity of individualized care. Conclusions: Standard prophylaxis regimens may not provide sufficient protection for all patients, particularly those with joint damage. A personalized treatment approach, targeting higher FLs when necessary, may be critical for optimizing outcomes.