Burosumab in adults with X-linked hypophosphatemia: real-world experience from a retrospective study in Sydney

X-linked hypophosphatemia (XLH) is a chronic disabling hereditary musculoskeletal disorder associated with inactivating <i>PHEX</i> mutations and elevated circulating FGF-23 concentrations. In a placebo-controlled trial of adults with XLH, burosumab (anti-FGF-23 antibody) demonstrated durable improvements in phosphate concentrations, and self-reported stiffness and physical limitation. However, real-world data regarding burosumab efficacy and tolerability in adults with XLH are lacking. A retrospective audit was performed of patients (age ≥18-years) who commenced 4-weekly subcutaneous burosumab for XLH at Royal North Shore and Westmead Hospitals, Sydney, between January 2021 and June 2024. Patients were managed per standard clinical care and burosumab dose adjusted as necessary according to manufacturer instructions. Electronic medical records were reviewed to collate data regarding patient demographics, XLH-related complications and prior treatment, burosumab dosage and side effects, and pre- and post-burosumab biochemistry and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores. Of the 13 adults with XLH, all had hypophosphatemia before commencing burosumab (mean 0.64 ± 0.08 mmol/L). Mean WOMAC scores demonstrated baseline impairments in stiffness, pain, and physical limitation. Burosumab was administered for median 15 months during follow-up (median dose 70 mg). Hypophosphatemia resolved in all patients within 3 months of burosumab (mean 1.03 ± 0.38 mmol/L). Two patients developed hyperphosphatemia 2 weeks after commencing burosumab requiring dose reduction. One patient ceased burosumab in the setting of hypercalcemia and constipation secondary to pre-existing tertiary hyperparathyroidism. Adverse events were mild, including transient musculoskeletal discomfort (<i>n</i> = 4), restless legs (<i>n</i> = 2), injection site reaction (<i>n</i> = 2), and headache (<i>n</i> = 1). Repeat WOMAC within 12 months of commencing burosumab (<i>n</i> = 9) demonstrated clinically meaningful improvements in stiffness (-33.3 ± 12.5, <i>p</i><.001) and physical function (-14.3 ± 16.2, <i>p</i>=.029). This study reports real-world outcomes of adults with XLH treated with burosumab. Clinical experience from 2 centers in Sydney supports trial findings that burosumab is well-tolerated and associated with improved serum phosphate concentrations and self-reported stiffness and physical function.