Introduction: Burosumab was approved for treatment of pediatric patients with X-linked hypophosphatemia (XLH). However, data on its efficacy in adolescents (age > 12 years) and in real-world settings are lacking.
Material and methods: Here we assess the effects of 12 months burosumab treatment on mineral homeostasis in 77 pediatric XLH patients (50 children, 27 adolescents) enrolled in the German XLH Registry. Age and sex related SD scores (SDS) were calculated for serum phosphate and alkaline phosphatase (ALP) levels, and renal tubular reabsorption of phosphate per glomerular filtration rate (TmP/GFR).
Results: At baseline, all patients presented with profound hypophosphatemia (-4.5 SDS), reduced TmP/GFR (-6.5 SDS), and elevated ALP (2.7 SDS, each P<0.001 vs healthy children) suggesting persisting rickets despite long-term therapy with oral phosphate and active vitamin D. Burosumab treatment resulted in rapid increases in mean serum phosphate and TmP/GFR by approx. 0.3 mmol/l amounting to -2.2 SDS and -2.5 SDS at 12 months, respectively (each P<0.001 vs baseline). This was paralleled by a continuous decrease in serum ALP (1.3 SDS, P<0.001 vs baseline). Serum phosphate, TmP/GFR, and ALP values were normalized in approximately 40%, 30% and 80% of patients, respectively. Two patients had transient hyperphosphatemia due to a dosing error. At 12 months, the median burosumab dosage amounted to 0.8 mg/kg (range 0.6-1.2). Serum phosphate levels at 12 months were comparable between children (-2.3 SDS) and adolescents (-2.1 SDS) and associated with parathyroid hormone (PTH) levels. Serum ALP z-scores were associated with PTH levels in adolescents but not in children.
Conclusions: In this real world setting 12 months burosumab treatment was effective to normalize serum ALP levels in children and adolescents with XLH suggesting healing of rickets despite persisting mild hypophosphatemia in about half of patients. Elevated PTH levels are a risk factor for failure to normalize mineral homeostasis.
15 Sep 2022 - 17 Sep 2022