PB0633 - Understanding the Requirement for Additional Factor VIII Infusion Associated with Novel Haemophilia A Treatments: An Expert Elicitation Exercise

Background: Severe haemophilia A (HA) is a congenital bleeding disorder characterised by spontaneous and traumatic bleeding episodes, currently managed with prophylactic factor VIII (FVIII) infusions or subcutaneous administration of non-factor therapy. Novel HA treatment approaches, such as gene therapy (GTx), offer possible reduction in clinical and treatment burden, however, evidence on supplemental FVIII use in people treated with non-factor or gene therapy is scarce.

Aims: To conduct a Sheffield Elicitation Framework (SHELF) exercise with UK clinical experts on proportion of severe HA patients requiring additional FVIII infusions while receiving prophylaxis with non-factor therapy or after the administration of gene therapy across levels of physical activity and joint damage.

Methods: A group of haematology experts estimated the requirement for factor infusions, in relation to breakthrough bleeds, in patients participating in ‘low-to-moderate’ or ‘moderate-to-high’ physical activity, with or without chronic joint damage measured by the problem joint (PJ) metric (0 PJs vs ≥1 PJs). The uncertainty around estimates was quantified using SHELF to construct a probability distribution representing expert input. Typical output is median, as presented here.

Results: Estimated proportion of patients requiring supplemental factor infusions ranged from 10% (median) for GTx patients with no PJs and low/moderate activity to 20% for patients receiving non-factor therapy with ≥1 PJs and ‘moderate-to-high’ activity (Table 1). Estimated number of supplemental factor infusions within a six-month period, in those requiring them, ranged from 1.8 in patients receiving non-factor therapy, 0 PJs, and ‘low-to-moderate’ activity, to 16 for non-factor therapy patients with ≥1 PJs and ‘moderate-to-high’ activity (Table 2).

Conclusion(s): Expert elicitation indicated the extent to which factor infusions may be required for the UK severe HA population treated with non-factor replacement or gene therapy. Of which, patients receiving non-factor therapy with ‘moderate-to-high’ physical activity and joint damage experienced higher burden of additional FVIII infusions in relation to breakthrough bleeds.