Effects of Burosumab Treatment on Mineral Metabolism in Children and Adolescents With X-linked Hypophosphatemia
© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
CONTEXT: Burosumab has been approved for the treatment of children and adults with X-linked hypophosphatemia (XLH). Real-world data and evidence for its efficacy in adolescents are lacking.
OBJECTIVE: To assess the effects of 12 months of burosumab treatment on mineral metabolism in children (aged <12 years) and adolescents (aged 12-18 years) with XLH.
DESIGN: Prospective national registry.
SETTING: Hospital clinics.
PATIENTS: A total of 93 patients with XLH (65 children, 28 adolescents).
MAIN OUTCOME MEASURES: Z scores for serum phosphate, alkaline phosphatase (ALP), and renal tubular reabsorption of phosphate per glomerular filtration rate (TmP/GFR) at 12 months.
RESULTS: At baseline, patients showed hypophosphatemia (-4.4 SD), reduced TmP/GFR (-6.5 SD), and elevated ALP (2.7 SD, each P < .001 vs healthy children) irrespective of age, suggesting active rickets despite prior therapy with oral phosphate and active vitamin D in 88% of patients. Burosumab treatment resulted in comparable increases in serum phosphate and TmP/GFR in children and adolescents with XLH and a steady decline in serum ALP (each P < .001 vs baseline). At 12 months, serum phosphate, TmP/GFR, and ALP levels were within the age-related normal range in approximately 42%, 27%, and 80% of patients in both groups, respectively, with a lower, weight-based final burosumab dose in adolescents compared with children (0.72 vs 1.06 mg/kg, P < .01).
CONCLUSIONS: In this real-world setting, 12 months of burosumab treatment was equally effective in normalizing serum ALP in adolescents and children, despite persistent mild hypophosphatemia in one-half of patients, suggesting that complete normalization of serum phosphate is not mandatory for substantial improvement of rickets in these patients. Adolescents appear to require lower weight-based burosumab dosage than children.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:108 |
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| Enthalten in: |
The Journal of clinical endocrinology and metabolism - 108(2023), 10 vom: 18. Sept., Seite e998-e1006 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ewert, Annika [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.09.2023 Date Revised 21.09.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1210/clinem/dgad223 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM356015602 |
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| 100 | 1 | |a Ewert, Annika |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effects of Burosumab Treatment on Mineral Metabolism in Children and Adolescents With X-linked Hypophosphatemia |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 19.09.2023 | ||
| 500 | |a Date Revised 21.09.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a CONTEXT: Burosumab has been approved for the treatment of children and adults with X-linked hypophosphatemia (XLH). Real-world data and evidence for its efficacy in adolescents are lacking | ||
| 520 | |a OBJECTIVE: To assess the effects of 12 months of burosumab treatment on mineral metabolism in children (aged <12 years) and adolescents (aged 12-18 years) with XLH | ||
| 520 | |a DESIGN: Prospective national registry | ||
| 520 | |a SETTING: Hospital clinics | ||
| 520 | |a PATIENTS: A total of 93 patients with XLH (65 children, 28 adolescents) | ||
| 520 | |a MAIN OUTCOME MEASURES: Z scores for serum phosphate, alkaline phosphatase (ALP), and renal tubular reabsorption of phosphate per glomerular filtration rate (TmP/GFR) at 12 months | ||
| 520 | |a RESULTS: At baseline, patients showed hypophosphatemia (-4.4 SD), reduced TmP/GFR (-6.5 SD), and elevated ALP (2.7 SD, each P < .001 vs healthy children) irrespective of age, suggesting active rickets despite prior therapy with oral phosphate and active vitamin D in 88% of patients. Burosumab treatment resulted in comparable increases in serum phosphate and TmP/GFR in children and adolescents with XLH and a steady decline in serum ALP (each P < .001 vs baseline). At 12 months, serum phosphate, TmP/GFR, and ALP levels were within the age-related normal range in approximately 42%, 27%, and 80% of patients in both groups, respectively, with a lower, weight-based final burosumab dose in adolescents compared with children (0.72 vs 1.06 mg/kg, P < .01) | ||
| 520 | |a CONCLUSIONS: In this real-world setting, 12 months of burosumab treatment was equally effective in normalizing serum ALP in adolescents and children, despite persistent mild hypophosphatemia in one-half of patients, suggesting that complete normalization of serum phosphate is not mandatory for substantial improvement of rickets in these patients. Adolescents appear to require lower weight-based burosumab dosage than children | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a TmP/GFR | |
| 650 | 4 | |a X-linked hypophosphatemia | |
| 650 | 4 | |a adolescents | |
| 650 | 4 | |a alkaline phosphatase | |
| 650 | 4 | |a burosumab | |
| 650 | 4 | |a children | |
| 650 | 4 | |a hyperparathyroidism | |
| 650 | 4 | |a phosphate | |
| 650 | 4 | |a rickets | |
| 650 | 7 | |a burosumab |2 NLM | |
| 650 | 7 | |a G9WJT6RD29 |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Phosphates |2 NLM | |
| 650 | 7 | |a Fibroblast Growth Factors |2 NLM | |
| 650 | 7 | |a 62031-54-3 |2 NLM | |
| 650 | 7 | |a Minerals |2 NLM | |
| 700 | 1 | |a Rehberg, Mirko |e verfasserin |4 aut | |
| 700 | 1 | |a Schlingmann, Karl Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Hiort, Olaf |e verfasserin |4 aut | |
| 700 | 1 | |a John-Kroegel, Ulrike |e verfasserin |4 aut | |
| 700 | 1 | |a Metzing, Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Wühl, Elke |e verfasserin |4 aut | |
| 700 | 1 | |a Schaefer, Franz |e verfasserin |4 aut | |
| 700 | 1 | |a Kemper, Markus J |e verfasserin |4 aut | |
| 700 | 1 | |a Derichs, Ute |e verfasserin |4 aut | |
| 700 | 1 | |a Richter-Unruh, Annette |e verfasserin |4 aut | |
| 700 | 1 | |a Patzer, Ludwig |e verfasserin |4 aut | |
| 700 | 1 | |a Albers, Norbert |e verfasserin |4 aut | |
| 700 | 1 | |a Dunstheimer, Desiree |e verfasserin |4 aut | |
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| 700 | 1 | |a Schröder, Carmen |e verfasserin |4 aut | |
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| 700 | 1 | |a Schnabel, Dirk |e verfasserin |4 aut | |
| 700 | 1 | |a Haffner, Dieter |e verfasserin |4 aut | |
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