Health-related quality of life in French adults with X-linked hypophosphatemia: real-world data from the International XLH Registry

Abstract X-linked hypophosphatemia is a rare genetic condition in which excess fibroblast growth factor 23 causes renal phosphate wasting, leading to skeletal morbidities. Patients experience musculoskeletal pain, stiffness, and fatigue, with impaired physical function and health-related quality of life. Burosumab has been available in France for the treatment of X-linked hypophosphatemia since 2021; European treatment guidelines suggest use in adults with pseudofractures or with insufficient response and/or intolerance to oral phosphate supplements and active vitamin D. The International XLH Registry is collecting long-term observational data in a real-world setting from patients with X-linked hypophosphatemia. Here, we report data from French adults from their first completion of the Short-form 36 version 2 health survey, a measure of health-related quality of life. The analysis used data from 123 adults who completed the survey at least once (73% women; mean age at completion 42.5 years [SD 13.4]; mean age at diagnosis 8.8 [12.6] years). Group mean T-scores in the current International XLH Registry sample were <47 on all Short-form 36 scale and summary scores, indicating impaired functioning. Physical and mental component summary scores were similar (43.0 [SD 9.1] vs 43.4 [11.3). Worse physical component summary scores were significantly related to older age (p=0.032), not working (excluding students) (p<0.001), history of fracture (p<0.001), lower-extremity fracture (p=0.010), surgery as an adult (p<0.001), current burosumab treatment (p=0.006), and previous burosumab treatment (p=0.002), possibly because treatment guidelines direct use to patients with more severe disease. Lower mental component summary scores were related to younger age (p=0.010). Physical summary scores were better in the current analysis than in adults with other chronic musculoskeletal conditions, mental summary scores were worse. Further exploration of the relationships between modifiable influences on HRQL is warranted, including the impact of earlier intervention with burosumab on physical symptoms, notably fractures, and health-related quality of life.