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 Eligibl...

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Main Authors: Karine Briot, Wei Sun, Rachel K Crowley, Maria Luisa Brandi, Stuart H Ralston, Peter Kamenický, Martine Cohen-Solal, Richard Keen, Angela Williams, Muhammad K Javaid, Robin H Lachmann, Annabel Nixon, Mark Nixon, Anne-Lise Lecoq, Sami Kolta, Jennifer S Walsh, Angela J Rylands
Format: Article
Language:English
Published: BMJ Publishing Group 2023-02-01
Series:RMD Open
Online Access:https://rmdopen.bmj.com/content/9/1/e002676.full
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author Karine Briot
Wei Sun
Rachel K Crowley
Maria Luisa Brandi
Stuart H Ralston
Peter Kamenický
Martine Cohen-Solal
Richard Keen
Angela Williams
Muhammad K Javaid
Robin H Lachmann
Annabel Nixon
Mark Nixon
Anne-Lise Lecoq
Sami Kolta
Jennifer S Walsh
Angela J Rylands
author_facet Karine Briot
Wei Sun
Rachel K Crowley
Maria Luisa Brandi
Stuart H Ralston
Peter Kamenický
Martine Cohen-Solal
Richard Keen
Angela Williams
Muhammad K Javaid
Robin H Lachmann
Annabel Nixon
Mark Nixon
Anne-Lise Lecoq
Sami Kolta
Jennifer S Walsh
Angela J Rylands
author_sort Karine Briot
collection DOAJ
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.
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spelling doaj.art-88b9695323e84af5a53817962185f3402023-03-01T11:00:17ZengBMJ Publishing GroupRMD Open2056-59332023-02-019110.1136/rmdopen-2022-002676Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatmentKarine Briot0Wei Sun1Rachel K Crowley2Maria Luisa Brandi3Stuart H Ralston4Peter Kamenický5Martine Cohen-Solal6Richard Keen7Angela Williams8Muhammad K Javaid9Robin H Lachmann10Annabel Nixon11Mark Nixon12Anne-Lise Lecoq13Sami Kolta14Jennifer S Walsh15Angela J Rylands16INSERM U1153, Paris, France1 Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, and Department of Orthopedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Endocrinology, St Vincent’s University Hospital, Dublin, IrelandFIRMO Foundation, Florence, ItalyRheumatology and Bone Diseases Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UKEndocrine Physiology and Pathophysiology, INSERM, Paris-Saclay University, Paris, FranceDepartment of Rheumatology, Hôpital Lariboisière, Paris, FranceMetabolic Bone Disease Unit, Royal National Orthopaedic Hospital NHS Trust, London, UKHealth Economics and Outcomes Research Department, Kyowa Kirin International PLC, Marlow, UKNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UKCharles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UKChilli Consultancy, Salisbury, UKChilli Consultancy, Salisbury, UK7 Centre de Recherche Clinique, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Paris, FranceINSERM U1153, Service de Rhumatologie, Hôpital Cochin, Paris, FranceDepartment of Oncology and Metabolism, The University of Sheffield, Sheffield, UKHealth Economics and Outcomes Research Department, Kyowa Kirin International PLC, Marlow, UKObjectives 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.https://rmdopen.bmj.com/content/9/1/e002676.full
spellingShingle Karine Briot
Wei Sun
Rachel K Crowley
Maria Luisa Brandi
Stuart H Ralston
Peter Kamenický
Martine Cohen-Solal
Richard Keen
Angela Williams
Muhammad K Javaid
Robin H Lachmann
Annabel Nixon
Mark Nixon
Anne-Lise Lecoq
Sami Kolta
Jennifer S Walsh
Angela J Rylands
Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment
RMD Open
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
url https://rmdopen.bmj.com/content/9/1/e002676.full
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