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Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment
OBJECTIVES: To report the impact of continued burosumab treatment on clinical laboratory tests of efficacy, patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia who continued from a 96-week phase 3 study into a 48-week open-label extension. METHODS: Elig...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980374/ https://www.ncbi.nlm.nih.gov/pubmed/36854566 http://dx.doi.org/10.1136/rmdopen-2022-002676 |
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author | Kamenicky, Peter Briot, Karine Brandi, Maria Luisa Cohen-Solal, Martine Crowley, Rachel K Keen, Richard Kolta, Sami Lachmann, Robin H Lecoq, Anne-Lise Ralston, Stuart H Walsh, Jennifer S Rylands, Angela J Williams, Angela Sun, Wei Nixon, Annabel Nixon, Mark Javaid, Muhammad K |
author_facet | Kamenicky, Peter Briot, Karine Brandi, Maria Luisa Cohen-Solal, Martine Crowley, Rachel K Keen, Richard Kolta, Sami Lachmann, Robin H Lecoq, Anne-Lise Ralston, Stuart H Walsh, Jennifer S Rylands, Angela J Williams, Angela Sun, Wei Nixon, Annabel Nixon, Mark Javaid, Muhammad K |
author_sort | Kamenicky, Peter |
collection | PubMed |
description | OBJECTIVES: To report the impact of continued burosumab treatment on clinical laboratory tests of efficacy, patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia who continued from a 96-week phase 3 study into a 48-week open-label extension. METHODS: Eligible participants from the phase 3 study continued on the burosumab regimen received at the end of the phase 3 study for a further 48 weeks (n=31). Some (not all) received compassionate burosumab treatment between the two studies (a period of 6–18 months). The primary efficacy outcome was fasting serum phosphate concentration; secondary outcomes were serum 1,25 dihydroxyvitamin D concentration, renal phosphate reabsorption, PROs and ambulatory function. RESULTS: Improvements in fasting serum phosphate, serum 1,25 dihydroxyvitamin D and renal phosphate reabsorption at 96 weeks were maintained through the 48-week extension. Improvements were also maintained in stiffness and physical function measured using the Western Ontario and McMaster Universities Osteoarthritis Index, pain and fatigue endpoints measuring using the Brief Pain Inventory short-form and Brief Pain Inventory, respectively, and in ambulatory function (6-Minute Walk Test). A post-hoc exploratory analysis exploring outcomes in participants who discontinued burosumab treatment between the studies (n=7) and those who received at least one dose (n=23) indicated that the benefits of burosumab on clinical laboratory tests of efficacy, PROs and ambulatory function may be lost when treatment is interrupted but recover over time when treatment is reinstated. CONCLUSION: Continued treatment with burosumab appears necessary for sustained clinical benefit. TRIAL REGISTRATION NUMBERS: Phase 3: NCT02526160; open-label extension: NCT03920072. |
format | Online Article Text |
id | pubmed-9980374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-99803742023-03-03 Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment Kamenicky, Peter Briot, Karine Brandi, Maria Luisa Cohen-Solal, Martine Crowley, Rachel K Keen, Richard Kolta, Sami Lachmann, Robin H Lecoq, Anne-Lise Ralston, Stuart H Walsh, Jennifer S Rylands, Angela J Williams, Angela Sun, Wei Nixon, Annabel Nixon, Mark Javaid, Muhammad K RMD Open Treatments OBJECTIVES: To report the impact of continued burosumab treatment on clinical laboratory tests of efficacy, patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia who continued from a 96-week phase 3 study into a 48-week open-label extension. METHODS: Eligible participants from the phase 3 study continued on the burosumab regimen received at the end of the phase 3 study for a further 48 weeks (n=31). Some (not all) received compassionate burosumab treatment between the two studies (a period of 6–18 months). The primary efficacy outcome was fasting serum phosphate concentration; secondary outcomes were serum 1,25 dihydroxyvitamin D concentration, renal phosphate reabsorption, PROs and ambulatory function. RESULTS: Improvements in fasting serum phosphate, serum 1,25 dihydroxyvitamin D and renal phosphate reabsorption at 96 weeks were maintained through the 48-week extension. Improvements were also maintained in stiffness and physical function measured using the Western Ontario and McMaster Universities Osteoarthritis Index, pain and fatigue endpoints measuring using the Brief Pain Inventory short-form and Brief Pain Inventory, respectively, and in ambulatory function (6-Minute Walk Test). A post-hoc exploratory analysis exploring outcomes in participants who discontinued burosumab treatment between the studies (n=7) and those who received at least one dose (n=23) indicated that the benefits of burosumab on clinical laboratory tests of efficacy, PROs and ambulatory function may be lost when treatment is interrupted but recover over time when treatment is reinstated. CONCLUSION: Continued treatment with burosumab appears necessary for sustained clinical benefit. TRIAL REGISTRATION NUMBERS: Phase 3: NCT02526160; open-label extension: NCT03920072. BMJ Publishing Group 2023-02-28 /pmc/articles/PMC9980374/ /pubmed/36854566 http://dx.doi.org/10.1136/rmdopen-2022-002676 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Treatments Kamenicky, Peter Briot, Karine Brandi, Maria Luisa Cohen-Solal, Martine Crowley, Rachel K Keen, Richard Kolta, Sami Lachmann, Robin H Lecoq, Anne-Lise Ralston, Stuart H Walsh, Jennifer S Rylands, Angela J Williams, Angela Sun, Wei Nixon, Annabel Nixon, Mark Javaid, Muhammad K Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment |
title | Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment |
title_full | Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment |
title_fullStr | Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment |
title_full_unstemmed | Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment |
title_short | Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment |
title_sort | benefit of burosumab in adults with x-linked hypophosphataemia (xlh) is maintained with long-term treatment |
topic | Treatments |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980374/ https://www.ncbi.nlm.nih.gov/pubmed/36854566 http://dx.doi.org/10.1136/rmdopen-2022-002676 |
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