SUN-753 Three-Year Evolution of X-Linked Hypophosphatemia in Children Treated with Burosumab: Predictive Factors for Dosing and Long-Term Outcomes

Abstract Disclosure: A. Linglart: None. J. Berkenou: None. A. Rothenbuhler: None. C. Audrain: None. D. Ertl: None. V.V. Zhukouskaya: None. Background: X-linked hypophosphatemia (XLH) is a rare metabolic bone disorder caused by mutations in the PHEX gene, leading to excessive fibroblast growth factor 23 (FGF23) activity, renal phosphate wasting, and impaired bone mineralization. Burosumab, a fully human monoclonal antibody targeting FGF23, has transformed XLH management by restoring phosphate homeostasis and improving skeletal outcomes. However, long-term data on disease progression, burosumab dosing, and associated complications in pediatric patients remain limited. Objective: To evaluate the evolution of XLH in children over a 3-year treatment period, identify predictive factors for burosumab dosing, and assess the incidence of long-term complications. Methods: This prospective monocentric longitudinal observational study followed a cohort of 67 pediatric patients (63% female) with XLH treated with burosumab for 3 years. At inclusion, 72% had a family history of XLH, and key comorbidities included craniosynostosis (37%), neurological complications (45%), and hearing loss (19%). The mean age at diagnosis was 0.9 ± 0.2 years, and prior phosphate and calcitriol therapy was received for an average of 6.8 ± 3.9 years. Results: As expected, burosumab treatment improved serum phosphate levels and ALP (alkaline phosphatase) levels. Burosumab dosing progressively increased from 0.45 ± 0.15 mg/kg at baseline to 1.35 ± 0.47 mg/kg at M12 (p<0.001) and remained stable thereafter. The mean cumulative burosumab dose reached 6245 ± 2736 mg at M60. Height SDS improved significantly from -1.39 ± 0.93 at baseline to -0.97 ± 0.88 at M36 (p<0.001),** with the most pronounced changes occurring in the first two years. Weight SDS increased significantly from -0.10 ± 0.96 to 0.16 ± 0.97 at M36 (p<0.001), while BMI SDS remained stable over time. Long-term complications showed improvement over time. The prevalence of nephrocalcinosis decreased from 45% at baseline to 21% at M36. Similarly, the incidence of hearing loss declined from 19% at baseline to 5% at M36. A multivariate regression model identified height SDS (β = 1.067, p = 0.0193) and BMI SDS (β = 0.960, p = 0.0272) as significant predictors of burosumab dose. ALP showed a trend toward significance (p = 0.0603). Age, sex, duration of conventional therapy, TRP, and TmP/eGFR were not significant predictors (p>0.05). Conclusion: Over 3 years, burosumab treatment led to expected sustained biochemical and skeletal improvements in children with XLH. The required burosumab dose was influenced by baseline height SDS and BMI SDS, suggesting that these factors may be useful for individualized dose adjustments. Additionally, long-term complications, such as nephrocalcinosis and hearing loss, showed a decreasing trend, suggesting the potential protective effects of burosumab. These findings provide valuable insights for tailoring long-term management strategies in pediatric XLH. Presentation: Sunday, July 13, 2025