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© 2023 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. http://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/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment
Author
Kamenicky, Peter 1   VIAFID ORCID Logo  ; Briot, Karine 2   VIAFID ORCID Logo  ; Brandi, Maria Luisa 3   VIAFID ORCID Logo  ; Cohen-Solal, Martine 4   VIAFID ORCID Logo  ; Crowley, Rachel K 5   VIAFID ORCID Logo  ; Keen, Richard 6 ; Kolta, Sami 7 ; Lachmann, Robin H 8   VIAFID ORCID Logo  ; Lecoq, Anne-Lise 9 ; Ralston, Stuart H 10   VIAFID ORCID Logo  ; Walsh, Jennifer S 11 ; Rylands, Angela J 12 ; Williams, Angela 12 ; Sun, Wei 13 ; Nixon, Annabel 14   VIAFID ORCID Logo  ; Nixon, Mark 14 ; Javaid, Muhammad K 15   VIAFID ORCID Logo 

 Service d'Endocrinologie et des Maladies de la Reproduction, Hôpital Bicêtre, Paris, France 
 Service de Rhumatologie, Hôpital Cochin, Paris, France 
 F.I.R.M.O. Foundation, Florence, Italy 
 INSERM U1132 BIOSCAR, Service de Rhumatologie, Hôpital Lariboisiere, Université de Paris, Paris, France 
 Rare Disease Clinical Trial Network, University College Dublin School of Medicine, Dublin, Ireland; Department of Endocrinology, St Vincent's University Hospital, Dublin, Ireland 
 Metabolic Bone Disease Unit, Royal National Orthopaedic Hospital, Stanmore, UK 
 INSERM U1153, Service de Rhumatologie, Hôpital Cochin, Paris, France 
 Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK 
 Physiologie et Physiopathologie Endocriniennes, Assistance Publique - Hôpitaux de Paris, Paris, France; Service d’Endocrinologie et des Maladies de la Reproduction, Hôpital Bicêtre, Paris, France 
10  Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK 
11  Department of Oncology and Metabolism, The University of Sheffield, Sheffield, UK 
12  Health Economics and Outcomes Research Department, Kyowa Kirin International PLC, Marlow, UK 
13  Biostatistics Department, Kyowa Kirin Pharmaceutical Development, Inc, Princeton, New Jersey, USA 
14  Chilli Consultancy, Salisbury, UK 
15  Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK 
First page
e002676
Section
Treatments
Publication year
2023
Publication date
Feb 2023
Publisher
BMJ Publishing Group LTD
e-ISSN
20565933
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2780474581
Copyright
© 2023 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. http://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/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.