Potential predictors of response to burosumab treatment in adult patients with X-Linked Hypophosphatemia

Background: X-linked hypophosphatemia (XLH) is a rare genetic condition characterized by elevated FGF23 levels, leading to chronic renal phosphate loss and persistent hypophosphatemia, which results in both skeletal and extraskeletal abnormalities. Burosumab, a human monoclonal antibody, inhibits FGF23 and has demonstrated effectiveness in correcting hypophosphatemia and improving disease outcomes. This study evaluated the efficacy of burosumab in adult patients with XLH and identified factors that may predict treatment response. Patients and Methods: Adult patients with XLH from an Italian cohort were treated with burosumab (1.0 mg/kg subcutaneously every 4 weeks) for up to 24 weeks. A subgroup analysis was performed on a smaller group of patients who were followed for up to 48 weeks. Clinical, biochemical, and patient-reported outcomes were analysed to identify potential predictors of treatment efficacy. Results: A total of 27 patients with XLH (mean age 42 years; 48% female) were included in the study. Following burosumab initiation, serum phosphate levels increased from a baseline median of 1.5 mg/dL (IQR 1.3-1.8) to 2.0 mg/dL (IQR 1.7-2.4) (p<0.05) in the overall population and remained higher than baseline at midpoints during the dosing interval for up to 24 weeks. Higher baseline serum phosphate predicted higher midpoint levels (p<0.05), whereas elevated baseline PTH (p<0.05) and FGF23 (p<0.001) were associated with lower phosphate levels. A subgroup analysis of 11 patients showed significant improvements in patient-reported outcomes for all participants. Moreover, improvements in WOMAC Pain (r=0.94, p=0.02) and BPI Worst Pain (r=0.98, p<0.001) were positively correlated with increased serum phosphate at week 48. Conclusion: In this real-world experience, burosumab effectively raised serum phosphate levels in XLH patients, with optimal levels observed in a subset of patients. Baseline serum phosphate, PTH, and iFGF23 were significant predictors of treatment response. Recognizing these predictors may assist in optimizing treatment strategies and improving patient management.