Adolescents’ experience of living with X-linked hypophosphataemia (XLH): a mixed-methods analysis of those who continued and discontinued burosumab treatment after end of skeletal growth

X-linked hypophosphataemia (XLH) is a rare, genetic, phosphate-wasting disorder caused by excess fibroblast growth factor 23 (FGF23). Children experience skeletal abnormalities, pain and impaired health-related quality of life (HRQL). The FGF23 inhibitor burosumab improved growth, decreased rickets severity and improved symptoms and HRQL in paediatric phase 3 trials. Using a mixed-methods approach, the MyXLH study aims to describe the lived experience of adolescents with XLH and to compare the experiences of adolescents who did and did not continue burosumab for the 26 weeks immediately after end of skeletal growth (EoSG), based on patient-reported daily activity, symptoms and HRQL, enriched with telephone interviews. Twenty-five adolescents were enrolled (16 girls, 9 boys) at centres in France, Germany, the Netherlands, Spain and the UK. EoSG (confirmed mostly by growth velocity and/or imaging) occurred at a mean (SD) age of 15.7 (1.3) years in girls and 17.2 (0.7) years in boys. Mean (SD) time on burosumab before EoSG was 4.3 (1.9) and 4.9 (2.6) years in those who continued and discontinued burosumab (n = 16 and 9), respectively. In adolescents who continued burosumab, serum phosphate levels remained stable after EoSG. Scores for Worst Pain, Worst Stiffness and Worst Fatigue were low and changed little, and physical activity (daily step count) was maintained. Mean EuroQol 5-dimension, 3-level youth (EQ-5D-Y-3 L) utility scores were 0.86 (0.24) before EoSG (n = 15) and 0.77 (0.30) after (n = 5). In interviews, these adolescents reported participating in school, physical and leisure activities; improvements in symptoms were linked to improved emotion. In adolescents who stopped burosumab at EoSG, phosphate levels decreased to below normal, scores for Worst Pain, Stiffness and Fatigue increased slightly (worse symptoms) but step count was broadly maintained. The mean (SD) EQ-5D-Y-3 L utility score decreased from 0.94 (0.10) before EoSG (n = 5) to 0.84 (0.15) (n = 3) after. Some adolescents reported worsening or newly emergent symptoms and reduced participation in school/work, physical and social activities. Some adolescents experienced detrimental effects on serum phosphate and functional XLH symptoms after stopping burosumab at EoSG; continuation of burosumab beyond EoSG may therefore be warranted to maintain symptom control.