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Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension

OBJECTIVES: To report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks. METHODS: Adults diagnosed with XLH were randomised 1:1 in a double-blinded trial to receive subcutaneous burosumab 1 mg/kg or pl...

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Autores principales: Briot, Karine, Portale, Anthony A, Brandi, Maria Luisa, Carpenter, Thomas O, Cheong, Hae Ii, Cohen-Solal, Martine, Crowley, Rachel K, Eastell, Richard, Imanishi, Yasuo, Ing, Steven, Insogna, Karl, Ito, Nobuaki, Jan de Beur, Suzanne, Javaid, Muhammad K, Kamenicky, Peter, Keen, Richard, Kubota, Takuo, Lachmann, Robin H, Perwad, Farzana, Pitukcheewanont, Pisit, Ralston, Stuart H, Takeuchi, Yasuhiro, Tanaka, Hiroyuki, Weber, Thomas J, Yoo, Han-Wook, Nixon, Annabel, Nixon, Mark, Sun, Wei, Williams, Angela, Imel, Erik A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458321/
https://www.ncbi.nlm.nih.gov/pubmed/34548383
http://dx.doi.org/10.1136/rmdopen-2021-001714
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author Briot, Karine
Portale, Anthony A
Brandi, Maria Luisa
Carpenter, Thomas O
Cheong, Hae Ii
Cohen-Solal, Martine
Crowley, Rachel K
Eastell, Richard
Imanishi, Yasuo
Ing, Steven
Insogna, Karl
Ito, Nobuaki
Jan de Beur, Suzanne
Javaid, Muhammad K
Kamenicky, Peter
Keen, Richard
Kubota, Takuo
Lachmann, Robin H
Perwad, Farzana
Pitukcheewanont, Pisit
Ralston, Stuart H
Takeuchi, Yasuhiro
Tanaka, Hiroyuki
Weber, Thomas J
Yoo, Han-Wook
Nixon, Annabel
Nixon, Mark
Sun, Wei
Williams, Angela
Imel, Erik A
author_facet Briot, Karine
Portale, Anthony A
Brandi, Maria Luisa
Carpenter, Thomas O
Cheong, Hae Ii
Cohen-Solal, Martine
Crowley, Rachel K
Eastell, Richard
Imanishi, Yasuo
Ing, Steven
Insogna, Karl
Ito, Nobuaki
Jan de Beur, Suzanne
Javaid, Muhammad K
Kamenicky, Peter
Keen, Richard
Kubota, Takuo
Lachmann, Robin H
Perwad, Farzana
Pitukcheewanont, Pisit
Ralston, Stuart H
Takeuchi, Yasuhiro
Tanaka, Hiroyuki
Weber, Thomas J
Yoo, Han-Wook
Nixon, Annabel
Nixon, Mark
Sun, Wei
Williams, Angela
Imel, Erik A
author_sort Briot, Karine
collection PubMed
description OBJECTIVES: To report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks. METHODS: Adults diagnosed with XLH were randomised 1:1 in a double-blinded trial to receive subcutaneous burosumab 1 mg/kg or placebo every 4 weeks for 24 weeks (NCT02526160). Thereafter, all subjects received burosumab every 4 weeks until week 96. PROs were measured using the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory (BFI), and ambulatory function was measured with the 6 min walk test (6MWT). RESULTS: Subjects (N=134) were randomised to burosumab (n=68) or placebo (n=66) for 24 weeks. At baseline, subjects experienced pain, stiffness, and impaired physical and ambulatory function. At week 24, subjects receiving burosumab achieved statistically significant improvement in some BPI-SF scores, BFI worst fatigue (average and greatest) and WOMAC stiffness. At week 48, all WOMAC and BPI-SF scores achieved statistically significant improvement, with some WOMAC and BFI scores achieving meaningful and significant change from baseline. At week 96, all WOMAC, BPI-SF and BFI achieved statistically significant improvement, with selected scores in all measures also achieving meaningful change. Improvement in 6MWT distance and percent predicted were statistically significant at all time points from 24 weeks. CONCLUSIONS: Adults with XLH have substantial burden of disease as assessed by PROs and 6MWT. Burosumab treatment improved phosphate homoeostasis and was associated with a steady and consistent improvement in PROs and ambulatory function. TRIAL REGISTRATION NUMBER: NCT02526160.
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spelling pubmed-84583212021-10-07 Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension Briot, Karine Portale, Anthony A Brandi, Maria Luisa Carpenter, Thomas O Cheong, Hae Ii Cohen-Solal, Martine Crowley, Rachel K Eastell, Richard Imanishi, Yasuo Ing, Steven Insogna, Karl Ito, Nobuaki Jan de Beur, Suzanne Javaid, Muhammad K Kamenicky, Peter Keen, Richard Kubota, Takuo Lachmann, Robin H Perwad, Farzana Pitukcheewanont, Pisit Ralston, Stuart H Takeuchi, Yasuhiro Tanaka, Hiroyuki Weber, Thomas J Yoo, Han-Wook Nixon, Annabel Nixon, Mark Sun, Wei Williams, Angela Imel, Erik A RMD Open Treatments OBJECTIVES: To report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks. METHODS: Adults diagnosed with XLH were randomised 1:1 in a double-blinded trial to receive subcutaneous burosumab 1 mg/kg or placebo every 4 weeks for 24 weeks (NCT02526160). Thereafter, all subjects received burosumab every 4 weeks until week 96. PROs were measured using the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory (BFI), and ambulatory function was measured with the 6 min walk test (6MWT). RESULTS: Subjects (N=134) were randomised to burosumab (n=68) or placebo (n=66) for 24 weeks. At baseline, subjects experienced pain, stiffness, and impaired physical and ambulatory function. At week 24, subjects receiving burosumab achieved statistically significant improvement in some BPI-SF scores, BFI worst fatigue (average and greatest) and WOMAC stiffness. At week 48, all WOMAC and BPI-SF scores achieved statistically significant improvement, with some WOMAC and BFI scores achieving meaningful and significant change from baseline. At week 96, all WOMAC, BPI-SF and BFI achieved statistically significant improvement, with selected scores in all measures also achieving meaningful change. Improvement in 6MWT distance and percent predicted were statistically significant at all time points from 24 weeks. CONCLUSIONS: Adults with XLH have substantial burden of disease as assessed by PROs and 6MWT. Burosumab treatment improved phosphate homoeostasis and was associated with a steady and consistent improvement in PROs and ambulatory function. TRIAL REGISTRATION NUMBER: NCT02526160. BMJ Publishing Group 2021-09-21 /pmc/articles/PMC8458321/ /pubmed/34548383 http://dx.doi.org/10.1136/rmdopen-2021-001714 Text en © Author(s) (or their employer(s)) 2021. 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
Briot, Karine
Portale, Anthony A
Brandi, Maria Luisa
Carpenter, Thomas O
Cheong, Hae Ii
Cohen-Solal, Martine
Crowley, Rachel K
Eastell, Richard
Imanishi, Yasuo
Ing, Steven
Insogna, Karl
Ito, Nobuaki
Jan de Beur, Suzanne
Javaid, Muhammad K
Kamenicky, Peter
Keen, Richard
Kubota, Takuo
Lachmann, Robin H
Perwad, Farzana
Pitukcheewanont, Pisit
Ralston, Stuart H
Takeuchi, Yasuhiro
Tanaka, Hiroyuki
Weber, Thomas J
Yoo, Han-Wook
Nixon, Annabel
Nixon, Mark
Sun, Wei
Williams, Angela
Imel, Erik A
Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension
title Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension
title_full Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension
title_fullStr Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension
title_full_unstemmed Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension
title_short Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension
title_sort burosumab treatment in adults with x-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension
topic Treatments
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458321/
https://www.ncbi.nlm.nih.gov/pubmed/34548383
http://dx.doi.org/10.1136/rmdopen-2021-001714
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