OBJECTIVES : X‑linked hypophosphataemia (XLH) is a rare, genetic, debilitating, chronic metabolic disease. A de novo cost-utility analysis was developed for the NICE Highly Specialised Technology assessment of burosumab in children and adolescents with XLH with a growing skeleton. The objective was to demonstrate the benefits of early treatment during childhood and model its consequent lifetime cost-effectiveness.

METHODS : A Markov model was developed comprising health-states using the Rickets Severity Score (healed, mild, moderate, severe) and all-cause death. The effectiveness of burosumab and standard of care (SoC) were obtained from clinical studies and a UK chart review. In the model, treatment with burosumab ceases once bone-growth ends and patients are assumed to remain in the same health state thereafter. A vignette study was conducted with UK clinical experts to describe patients in each health state across various age bands and to generate associated utilities.

RESULTS : Over a lifetime, SoC patients were equally distributed over the mild, moderate or severe states, whilst 70% of patients treated with burosumab were in the healed state. The vignette study indicated that quality of life declined across all health states with accumulating lifelong symptoms, but deterioration was faster in patients with rickets at closure of growth plates. The base case ICER of burosumab compared to SoC was £149,565 (£170,000 to £355,000 in deterministic sensitivity analysis). Including carer disutility reduced the ICER to £112,517.

CONCLUSIONS : Generation of utilities to support the evaluation was critical. In the absence of transition probabilities in adulthood, this included proxy utilities for long-term patient outcomes. Vignettes captured the complexity of XLH in children and adolescents, providing utilities in the absence of clinical trial data. The analysis is unlikely to have captured all complexities of XLH but nonetheless provides a suitable indication of the lifetime benefit of correcting skeletal structural deformity during growth.