Real-world Impact of Treatment on Growth in Children With X-Linked Hypophosphatemia

Context X-linked hypophosphatemia (XLH) is a rare, genetic, progressive, lifelong disorder manifest by impaired growth and disproportionate short stature. Burosumab, a monoclonal antibody against fibroblast growth factor 23, is approved for treating patients with XLH. Objective To understand the impact of burosumab treatment on growth in a real-world setting. Design Interim data from three ongoing, real-world observational studies (NCT03651505, NCT03193476, NCT03745521), were unified into a single study (APEX). Setting Outpatient clinics. Patients Children aged 2-17 years with XLH. Intervention(s) Subcutaneous burosumab versus oral phosphate salts and active vitamin D or no treatment. Main Outcome Measure(s) Retrospective and prospective height data from children enrolled in APEX were analyzed to provide long-term estimation of the impact of treatment on growth. Growth and height were estimated by a mixed regression model with separate models for children and adolescents. Results In total, 641 participants were analyzed (402 female) with 498 burosumab-treated and 143 burosumab-naïve. Median (interquartile range [IQR]) enrollment ages were 8 (5-12) years for burosumab-treated and 10 (4-14) years for burosumab-naïve participants. Burosumab-treated participants experienced improved growth over burosumab-naïve participants (additional growth velocity: 0.085 Z-score/year for children [P < 0.0001]; 0.121 Z-score/year for adolescents [P < 0.0001]). Modeling predicted greater adult height among burosumab-treated participants. Conclusion Burosumab had a robust, positive association with improved growth outcomes in male and female children and adolescents with XLH. Modeling based on a median of 3.3 years of follow-up predicted burosumab can support improvement of growth that will likely result in greater adult height.