基因治疗对“无血友病之忧心态”的影响：GENEr8-1试验参与者接受valoctocogene roxaparvovec治疗前后的结局

INTRODUCTION: Haemophilia-free mind is an aspirational concept defined as a state in which affected individuals are liberated from physical, mental, and treatment burdens of haemophilia. A conceptual framework has been proposed for the haemophilia-free mind that comprises ten dimensions.

AIM: To evaluate changes in achievement towards a haemophilia-free mind in participants with haemophilia A who received valoctocogene roxaparvovec gene therapy in the GENEr8-1 trial (NCT03370913), by confirming relevant dimensions, with measures and thresholds for each.

METHODS: An expert panel comprising four haemophilia clinicians and one patient expert identified dimensions of the haemophilia-free mind relevant to gene therapy. Measures and thresholds were defined for each dimension and used to analyse GENEr8-1 data to determine the proportion of participants achieving these thresholds at Baseline and Week 208.

RESULTS: The expert panel confirmed 7/10 dimensions as appropriate for use in gene therapy trials and defined measurement thresholds for each dimension. Among GENEr8-1 trial participants, improvements were observed across all seven dimensions. The proportion of participants with zero treated bleeds increased from 33% (Baseline) to 54% (Week 208). Similarly, those reporting no exogenous factor VIII use rose from 0% to 33%. Improvements in perceived burden on family members, physical activity, and travel were 8%, 16%, and 18%, respectively.

CONCLUSION: This expert-led analysis demonstrates application of the haemophilia-free mind framework to clinical trial data using existing outcome measures. Mapping GENEr8-1 data to this framework demonstrated improvements of up to 33% in domains that contribute towards a haemophilia-free mind in participants after valoctocogene roxaparvovec treatment.