Real-world Effectiveness of Burosumab Across Age Groups: X-linked Hypophosphatemia (XLH) Disease Monitoring Program.

Abstract

X-linked hypophosphatemia (XLH) is a rare disorder characterized by excess fibroblast growth factor 23 (FGF23), leading to chronic hypophosphatemia, osteomalacia, and rickets. To evaluate outcomes up to 3 years following initiation of treatment with anti-FGF23 antibody (burosumab) in a real-world setting among individuals with XLH, stratified by age group, including those excluded from clinical trials (< 1, 13-17, and ≥ 65 years). The XLH Disease Monitoring Program is a prospective, longitudinal, long-term-outcomes program for individuals with XLH. This analysis included participants who were burosumab-naive at baseline and who had initiated burosumab between baseline and the Year 1 visit. Changes from baseline in biochemistry, clinical outcomes, and patient-reported outcomes (PROs) were assessed at Year 1 (Y1) and Year 3 (Y3) visits. Among participants (n = 139), burosumab led to significant and sustained improvements in mean (SD) serum phosphate z-scores at Y1 and Y3 (change from baseline: 1.4 [1.1]; P < .0001 for each timepoint). Among pediatric participants, serum alkaline phosphatase z-scores, Rickets Severity Scores, and patient-reported pain interference declined significantly at Y1 and Y3; non-significant changes were observed in fatigue and physical function mobility. Adults showed significant improvements in PRO measures of pain, stiffness, and physical function, with higher proportions of participants achieving minimal clinically important differences at Y3 vs Y1. Trends observed in overall cohorts were generally consistent across age sub-groups, with statistical significance reached for many endpoints. This analysis demonstrated the real-world effectiveness of burosumab for XLH, which appears evident across age groups.