Effects of Burosumab Treatment on Mineral Metabolism in Children and Adolescents With X-linked Hypophosphatemia
Annika Ewert, Mirko Rehberg, Karl P. Schlingmann, Olaf Hiort, Ulrike John-Kroegel, Oliver Metzing, Elke Wühl, Franz Schaefer, Markus J. Kemper, Ute Derichs, Annette Richter-Unruh, Ludwig Patzer, Norbert Albers, Désirée Dunstheimer, Holger Haberland, Sabine Heger, Carmen Schröder, Norbert Jorch, Elmar Schmid, Hagen Staude, Marcus Weitz, Clemens Freiberg, Maren Leifheit‐Nestler, Miroslav Živičnjak, Dirk Schnabel, Dieter Haffner
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 are lacking. OBJECTIVE: To assess the effects of 12 months of 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: A total of 93 patients with XLH (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 < .001 vs 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 < .001 vs 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 with children (0.72 vs 1.06 mg/kg, P < .01). CONCLUSIONS: 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 one-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.