Overview of Patient-Reported Outcomes in Haemophilia Gene Therapy

Background: Three adeno-associated virus (AAV)-based gene therapies for haemophilia have received regulatory approval in Western countries since 2022, yet commercial uptake has been slow. Traditional clinical endpoints—annualised bleeding rate and factor activity levels—document haemostatic efficacy, but fail to capture what matters most to patients. Both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) increasingly recognise patient-reported outcomes (PROs) as meaningful endpoints for regulatory and health technology assessment decisions. Summary: Narrative review of peer-reviewed literature in PubMed and Web of Science (2017–2026) covering PRO instruments, clinical trial evidence, cost-effectiveness analyses, and qualitative patient data in haemophilia gene therapy. Six trials have reported PRO data using a total of 12 different instruments, of which five principal measures of which five measures are central to the quality-of-life evidence: the disease-specific Haem-A-QoL and Haemo-QoL-A, the generic EQ-5D-5L, and the gene therapy–specific coreHEM Mental Health Outlook (coreHEM-MHO). Across all studies, gene therapy produced clinically meaningful improvements in quality of life. Total disease specific quality of life scores improved by 6 to 15 points across trials—exceeding established clinically important difference thresholds—with the largest gains in the Treatment and Dealing with Haemophilia domains. EQ-5D-5L utility indices increased significantly in multiple trials. In the SPK-9001 long-term follow-up, durable Haem-A-QoL gains were confirmed through 156 weeks. The coreHEM-MHO, developed to capture psychological dimensions unique to gene therapy such as durability anxiety and disease identity adjustment, has been piloted in BENEGENE-2. Qualitative interviews documented profound reductions in treatment burden and improved daily functioning. Key Messages: PRO evidence consistently demonstrates that haemophilia gene therapy delivers quality-of-life benefits that extend well beyond what traditional clinical endpoints capture. These PRO-derived improvements are also the principal driver of gene therapy’s economic value, since cost-effectiveness models show substantial gains in health-related quality of life but negligible gains in life expectancy. Priorities include standardised coreHEM measurement, long-term registries, and ensuring certified haemophilia centres are equipped for systematic PRO follow-up.