OBJECTIVES: AADC deficiency is a rare disease with a wide range of symptoms including movement disorders, developmental delays, and autonomic symptoms from birth. Information on the impact of gene therapy on patients’ disease trajectory along with the associated benefits in terms of survival, quality of life and associated costs are limited. A cost-effectiveness model has been developed, based on motor-milestones, to estimate the long-term benefits of patients after treatment with gene therapy compared to those on current best supportive care (BSC).

METHODS: A Markov model approach is taken with a lifetime horizon. The model takes an NHS and social services perspective. Structurally, the model consists of two parts: the developmental phase, where patients starting from the no motor function state can progress to other motor milestone states, and a long-term phase based on extrapolations.

The efficacy for gene therapy is derived from modelling clinical trial data with duration up to 108 months (median: 5 years). Due to the extremely low incidence of AADC deficiency, there is a lack of data for key model inputs. Proxy diseases were used to estimate survival by motor milestone. Quality of life inputs were based on a disease-specific utility study. A European burden of illness study provided inputs on resource utilization to estimate disease management costs. Costs were taken from public sources.

RESULTS: The model indicates clear survival and quality of life benefits (17.30 undiscounted QALYs gained) for patients treated with gene therapy compared to BSC. Cost benefits were found for medication and resource usage. Scenario analyses indicate results remain robust while changing key inputs including time horizon, efficacy model, survival source and utility values.

CONCLUSIONS: This study provides a model that can explore long-term outcomes for patients with AADC deficiency indicating clear survival and quality of life benefits from gene therapy compared to BSC.