Effects of burosumab treatment on mineral metabolism in children and adolescents with X-linked hypophosphatemia

Abstract

Abstract Context Burosumab has been approved for the treatment of children and adults with X-linked hypophosphatemia (XLH). Real-world data and evidence for its efficacy in adolescents is lacking. Objective To assess the effects of 12 months burosumab treatment on mineral metabolism in children (aged < 12 years) and adolescents (aged 12-18 years) with XLH. Design Prospective national registry. Setting Hospital clinics. Patients 93 XLH patients (65 children, 28 adolescents). Main outcome measures Z-scores for serum phosphate, alkaline phosphatase (ALP), and renal tubular reabsorption of phosphate per glomerular filtration rate (TmP/GFR) at 12 months. Results At baseline, patients showed hypophosphatemia (-4.4 SD), reduced TmP/GFR (-6.5 SD) and elevated ALP (2.7 SD, each p < 0.001 versus healthy children) irrespective of age, suggesting active rickets despite prior therapy with oral phosphate and active vitamin D in 88% of patients. Burosumab treatment resulted in comparable increases in serum phosphate and TmP/GFR in children and adolescents with XLH, and a steady decline in serum ALP (each p < 0.001 versus baseline). At 12 months, serum phosphate, TmP/GFR, and ALP levels were within the age-related normal range in approximately 42%, 27% and 80% of patients in both groups, respectively, with a lower, weight-based final burosumab dose in adolescents compared to children (0.72 versus 1.06 mg/kg, p < 0.01). Conclusion In this real-world setting, 12 months of burosumab treatment was equally effective in normalizing serum ALP in adolescents and children, despite persistent mild hypophosphatemia in half of patients, suggesting that complete normalization of serum phosphate is not mandatory for substantial improvement of rickets in these patients. Adolescents appear to require lower weight-based burosumab dosage than children.