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Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia

PURPOSE: In X-linked hypophosphatemia (XLH), excess fibroblast growth factor-23 causes hypophosphatemia and low calcitriol, leading to musculoskeletal disease with clinical consequences. XLH treatment options include conventional oral phosphate with active vitamin D, or monotherapy with burosumab, a...

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Autores principales: Linglart, Agnès, Imel, Erik A, Whyte, Michael P, Portale, Anthony A, Högler, Wolfgang, Boot, Annemieke M, Padidela, Raja, van’t Hoff, William, Gottesman, Gary S, Chen, Angel, Skrinar, Alison, Scott Roberts, Mary, Carpenter, Thomas O
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851952/
https://www.ncbi.nlm.nih.gov/pubmed/34636899
http://dx.doi.org/10.1210/clinem/dgab729
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author Linglart, Agnès
Imel, Erik A
Whyte, Michael P
Portale, Anthony A
Högler, Wolfgang
Boot, Annemieke M
Padidela, Raja
van’t Hoff, William
Gottesman, Gary S
Chen, Angel
Skrinar, Alison
Scott Roberts, Mary
Carpenter, Thomas O
author_facet Linglart, Agnès
Imel, Erik A
Whyte, Michael P
Portale, Anthony A
Högler, Wolfgang
Boot, Annemieke M
Padidela, Raja
van’t Hoff, William
Gottesman, Gary S
Chen, Angel
Skrinar, Alison
Scott Roberts, Mary
Carpenter, Thomas O
author_sort Linglart, Agnès
collection PubMed
description PURPOSE: In X-linked hypophosphatemia (XLH), excess fibroblast growth factor-23 causes hypophosphatemia and low calcitriol, leading to musculoskeletal disease with clinical consequences. XLH treatment options include conventional oral phosphate with active vitamin D, or monotherapy with burosumab, a monoclonal antibody approved to treat children and adults with XLH. We have previously reported outcomes up to 64 weeks, and here we report safety and efficacy follow-up results up to 160 weeks from an open-label, multicenter, randomized, dose-finding trial of burosumab for 5- to 12-year-old children with XLH. METHODS: After 1 week of conventional therapy washout, patients were randomized 1:1 to burosumab every 2 weeks (Q2W) or every 4 weeks (Q4W) for 64 weeks, with dosing titrated based on fasting serum phosphorus levels between baseline and week 16. From week 66 to week 160, all patients received Q2W burosumab. RESULTS: Twenty-six children were randomized initially into each Q2W and Q4W group and all completed treatment to week 160. In 41 children with open distal femoral and proximal tibial growth plates (from both treatment groups), total Rickets Severity Score significantly decreased by 0.9 ± 0.1 (least squares mean ± SE; P < 0.0001) from baseline to week 160. Fasting serum phosphorus increases were sustained by burosumab therapy throughout the study, with an overall population mean (SD) of 3.35 (0.39) mg/dL, within the pediatric normal range (3.2-6.1 mg/dL) at week 160 (mean change from baseline P < 0.0001). Most adverse events were mild to moderate in severity. MAIN CONCLUSIONS: In children with XLH, burosumab administration for 160 weeks improved phosphate homeostasis and rickets and was well-tolerated. Long-term safety was consistent with the reported safety profile of burosumab. CLINICALTRIALS.GOV: NCT02163577
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spelling pubmed-88519522022-02-18 Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia Linglart, Agnès Imel, Erik A Whyte, Michael P Portale, Anthony A Högler, Wolfgang Boot, Annemieke M Padidela, Raja van’t Hoff, William Gottesman, Gary S Chen, Angel Skrinar, Alison Scott Roberts, Mary Carpenter, Thomas O J Clin Endocrinol Metab Clinical Research Article PURPOSE: In X-linked hypophosphatemia (XLH), excess fibroblast growth factor-23 causes hypophosphatemia and low calcitriol, leading to musculoskeletal disease with clinical consequences. XLH treatment options include conventional oral phosphate with active vitamin D, or monotherapy with burosumab, a monoclonal antibody approved to treat children and adults with XLH. We have previously reported outcomes up to 64 weeks, and here we report safety and efficacy follow-up results up to 160 weeks from an open-label, multicenter, randomized, dose-finding trial of burosumab for 5- to 12-year-old children with XLH. METHODS: After 1 week of conventional therapy washout, patients were randomized 1:1 to burosumab every 2 weeks (Q2W) or every 4 weeks (Q4W) for 64 weeks, with dosing titrated based on fasting serum phosphorus levels between baseline and week 16. From week 66 to week 160, all patients received Q2W burosumab. RESULTS: Twenty-six children were randomized initially into each Q2W and Q4W group and all completed treatment to week 160. In 41 children with open distal femoral and proximal tibial growth plates (from both treatment groups), total Rickets Severity Score significantly decreased by 0.9 ± 0.1 (least squares mean ± SE; P < 0.0001) from baseline to week 160. Fasting serum phosphorus increases were sustained by burosumab therapy throughout the study, with an overall population mean (SD) of 3.35 (0.39) mg/dL, within the pediatric normal range (3.2-6.1 mg/dL) at week 160 (mean change from baseline P < 0.0001). Most adverse events were mild to moderate in severity. MAIN CONCLUSIONS: In children with XLH, burosumab administration for 160 weeks improved phosphate homeostasis and rickets and was well-tolerated. Long-term safety was consistent with the reported safety profile of burosumab. CLINICALTRIALS.GOV: NCT02163577 Oxford University Press 2021-10-12 /pmc/articles/PMC8851952/ /pubmed/34636899 http://dx.doi.org/10.1210/clinem/dgab729 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Clinical Research Article
Linglart, Agnès
Imel, Erik A
Whyte, Michael P
Portale, Anthony A
Högler, Wolfgang
Boot, Annemieke M
Padidela, Raja
van’t Hoff, William
Gottesman, Gary S
Chen, Angel
Skrinar, Alison
Scott Roberts, Mary
Carpenter, Thomas O
Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia
title Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia
title_full Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia
title_fullStr Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia
title_full_unstemmed Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia
title_short Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia
title_sort sustained efficacy and safety of burosumab, a monoclonal antibody to fgf23, in children with x-linked hypophosphatemia
topic Clinical Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851952/
https://www.ncbi.nlm.nih.gov/pubmed/34636899
http://dx.doi.org/10.1210/clinem/dgab729
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