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Multicenter Study
. 2025 Aug;48(8):1857-1869.
doi: 10.1007/s40618-025-02596-3. Epub 2025 May 5.

Predictors of response to burosumab in adults with X-linked hypophosphatemia: real-world data from an Italian cohort

Gaetano Paride Arcidiacono  1 , Valentina Camozzi  2 , Giovanni Tripepi  3 , Cristina Eller-Vainicher  4 , Giuseppe Vezzoli  5 , Maria Luisa Brandi  6 , Gemma Marcucci  7 , Giuseppe Girasole  8 , Antonio Aversa  9 , Corrado Vitale  10 , Gaetana Cerbone  11 , Maria Michela D'Alessandro  12 , Martina Zaninotto  13 , Maria Fusaro  14   15 , Marco Onofrio Torres  1 , Michele Cannito  2 , Alberta Cecchinato  1 , Martin Diogo  1 , Mor Peleg Falb  1 , Francesca Guidolin  1 , Marta Zampogna  4 , Mario Plebani  13 , Elena Campello  1 , Paolo Simioni  1 , Stefania Sella  16 , Sandro Giannini  1
Affiliations
Multicenter Study

Predictors of response to burosumab in adults with X-linked hypophosphatemia: real-world data from an Italian cohort

Gaetano Paride Arcidiacono et al. J Endocrinol Invest. 2025 Aug.

Abstract

Purpose: X-linked hypophosphatemia (XLH) is a genetic disorder characterized by elevated FGF23 levels, leading to phosphate wasting and hypophosphatemia, causing skeletal and extraskeletal abnormalities. Burosumab, an antibody targeting FGF23, improves hypophosphatemia and clinical outcomes. This study evaluated the real-world efficacy of burosumab and identify predictors of treatment response.

Methods: Twenty-seven adult XLH patients (mean age 42 years; 48% female) from an Italian multicenter cohort were treated with burosumab for up to 24 weeks. Laboratory tests were evaluated at midpoints and endpoints (14 and 28 days) of the dosing interval. In a subset of patients (N = 11) followed for 48 weeks, laboratory tests and patient-reported outcomes were also assessed.

Results: After initiating burosumab, median serum phosphate levels increased from 1.5 mg/dL (IQR 1.3-1.8) to 2.0 mg/dL (IQR 1.7-2.4) (p < 0.05), remaining higher than baseline at the midpoints of the dosing interval for up to 24 weeks. Higher baseline phosphate predicted higher midpoint levels (p < 0.05), whereas higher baseline PTH (p < 0.05) and FGF23 (p < 0.001) were associated with lower phosphate levels at midpoints. In patients (N = 11) followed for 48 weeks, significant improvements in patient-reported outcomes in all patients were observed. Both WOMAC Pain (r = 0.94, p = 0.02) and BPI Worst Pain (r = 0.98, p < 0.001) were positively correlated with increased phosphate at week 48.

Conclusion: Burosumab effectively increased serum phosphate levels and improved clinical outcomes in a real-world setting, particularly in patients with more substantial increases in serum phosphate levels. Baseline serum phosphate, PTH, and FGF23 levels predicted response, helping tailor treatment strategies and improve long-term patient management.

Keywords: Burosumab; FGF23; Patient-reported outcomes; Real-life; Serum phosphate; X-linked hypophosphatemia.

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Conflict of interest statement

Declarations. Conflict of interest: GM: Kyowa Kirin consultation. All other authors have no conflict of interest to declare. Ethical approval: This study was performed in accordance with the 1964 Helsinki declaration and its later amendments and was authorized by the Ethics Committee (Comitato Etico Territoriale Area Centro-Est Veneto, 391n/AO/23). The committee provided ethical approval for the research protocol, ensuring that the study complies with the ethical standards for research involving human participants. Informed consent: All participants provided written informed consent to their participation after being informed about the study’s nature and purpose.

Figures

Fig. 1
Fig. 1
Trends in serum phosphate up to week 24, comparing each timepoint with baseline. * represents a p-value of < 0.05, ** = p < 0.01 and *** = p < 0.001
Fig. 2
Fig. 2
Effect of burosumab on serum phosphate (A), TmP/GFR (B), serum calcium (C) and bALP (D) up to week 48. * represents a p-value of < 0.05, ** = p < 0.01 and *** = p < 0.001. bALP = bone alkaline phosphatase, TmP/GFR = tubular maximum phosphate reabsorption per glomerular filtration rate
Fig. 3
Fig. 3
Patient-reported outcome scores after burosumab treatment are shown at baseline and at week 48 for the following measures: WOMAC Pain (A), WOMAC Stiffness (B), WOMAC Physical Function (C), WOMAC Overall (D), BPI Worst Pain (E), BPI Average Pain (F), BPI Pain Interference (G), HAQ (H), RAPID3 Function (I), RAPID3 Pain (J), RAPID3 Patient Global Estimate (K), and RAPID3 Overall (L). BPI = The Brief Pain Inventory, HAQ = Health Assessment Questionnaire, RAPID3 = Routine Assessment of Patient Index Data 3, WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index. * represents a p-value of < 0.05, ** = p < 0.01 and *** = p < 0.001
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