Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Adult Patients with X-Linked Hypophosphatemia

Dalal S Ali; Reza D Mirza; Farah Alsarraf; Salma Hussein; Hajar Abu Alrob; Natasha M Appelman-Dijkstra; Signe Sparre Beck-Nielsen; Martin Biosse-Duplan; Maria Luisa Brandi; Thomas O Carpenter; Catherine Chaussain; Martine Cohen-Solal; Rachel K Crowley; Karel Dandurand; Pablo Florenzano; Seiji Fukumoto; Claudia Gagnon; Paul Goodyer; Corinna Grasemann; Erik A Imel; Suzanne M Jan de Beur; Anna Lehman; E Michael Lewiecki; Emmett Morgante; Leanne M Ward; Aliya A Khan; Gordon Guyatt

doi:10.1210/clinem/dgae890

Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Adult Patients with X-Linked Hypophosphatemia

J Clin Endocrinol Metab. 2024 Dec 23:dgae890. doi: 10.1210/clinem/dgae890. Online ahead of print.

Authors

Dalal S Ali¹, Reza D Mirza², Farah Alsarraf¹, Salma Hussein¹, Hajar Abu Alrob², Natasha M Appelman-Dijkstra³, Signe Sparre Beck-Nielsen^{4

5}, Martin Biosse-Duplan⁶, Maria Luisa Brandi⁷, Thomas O Carpenter⁸, Catherine Chaussain⁹, Martine Cohen-Solal¹⁰, Rachel K Crowley¹¹, Karel Dandurand¹², Pablo Florenzano¹³, Seiji Fukumoto¹⁴, Claudia Gagnon¹⁵, Paul Goodyer¹⁶, Corinna Grasemann¹⁷, Erik A Imel¹⁸, Suzanne M Jan de Beur¹⁹, Anna Lehman²⁰, E Michael Lewiecki²¹, Emmett Morgante²², Leanne M Ward²³, Aliya A Khan¹, Gordon Guyatt^{2

24

25}

Affiliations

¹ Division of Endocrinology and Metabolism, McMaster University.
² Department of Health Research Methods, Evidence, and Impact, McMaster University.
³ Department of Internal Medicine, Division of Endocrinology, Center for Bone Quality, Leiden University Medical Center, Leiden, the Netherlands.
⁴ Centre for Rare Diseases, Aarhus University Hospital, Aarhus, Denmark.
⁵ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁶ Faculty of Dentistry, Université Paris Cité, Paris, France; Institut Imagine, INSERM 1163, Paris, France; APHP, Paris, France.
⁷ Vita-Salute San Raffaele University, Milan, Italy.
⁸ Departments of Pediatrics (Endocrinology), and Orthopedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, USA.
⁹ Faculty of Dentistry, Université Paris Cité and APHP, Paris, France.
¹⁰ Department of Rheumatology and Reference Center for Rare Bone Diseases, hopital Lariboisiere, Paris, France.
¹¹ Rare Disease Clinical Trial Network, University College Dublin, Ireland.
¹² Université de Sherbrooke, Sherbrooke, Québec, Canada.
¹³ Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile.
¹⁴ Tamaki-Aozora Hospital, Japan.
¹⁵ Department of Medicine, Université Laval, Quebec City, Canada; CHU de Québec-Université Laval Research Centre, Quebec City, Canada.
¹⁶ Research Institute of the McGill University Health Centre, Montreal, Canada.
¹⁷ Department of Pediatrics, Division of Rare Diseases, Katholisches Klinikum Bochum and Ruhr-University Bochum, Bochum, Germany.
¹⁸ Department of Medicine and Pediatrics, Indiana University School of Medicine.
¹⁹ University of Virginia School of Medicine, Charlottesville, VA, USA.
²⁰ University of British Columbia; Adult Metabolic Diseases Clinic, Vancouver, BC, Canada.
²¹ New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA.
²² University of Waterloo, Waterloo, ON, Canada.
²³ Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.
²⁴ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
²⁵ MAGIC Evidence Ecosystem Foundation [ www.magicevidence.org ], Lovisenberggata 17C, 0456 Oslo, Norway.

PMID: 39715351
DOI: 10.1210/clinem/dgae890

Abstract

Objective: To examine the highest certainty evidence addressing the management of X-linked hypophosphatemia (XLH) in adults to inform treatment recommendations.

Methods: We searched Embase, MEDLINE, Web of Science, and Cochrane Central up to May 2023. Eligible studies included RCTs and observational studies of individuals 18+ with clinically or genetically confirmed XLH. Manuscripts comparing burosumab to no treatment or conventional therapy (phosphate and active vitamin D) and conventional therapy to no treatment were included. Two reviewers independently determined eligibility, extracted data, and assessed risk of bias (RoB). GRADE methodology was used to assess evidence certainty.

Results: We screened 4,114 records, after removing duplicates, and assessed 254 full texts. One RCT and two observational studies were eligible. The RCT of burosumab versus no treatment had low RoB. Burosumab probably improves pain from fracture/pseudofracture healing (moderate certainty) but has little or no impact on direct pain measures (moderate certainty). Burosumab may reduce the need for parathyroidectomy (low certainty) but has little or no impact on fatigue (high certainty), stiffness (moderate certainty), and mobility (low certainty) over 24 weeks. Burosumab may increase dental abscess risk (low certainty). Indirect evidence comparing burosumab to conventional therapy provided low certainty regarding burosumab versus conventional therapy. Two observational studies on conventional therapy versus no treatment had high RoB and very low certainty regarding the impact of conventional therapy on patient-important outcomes.

Conclusion: No formal comparisons between burosumab and conventional therapy in adults exist. Evidence for conventional therapy versus no treatment is very uncertain. Our review highlights the need for more data on the long-term effects of burosumab and conventional therapy on patient-important outcomes in adult patients with XLH.

Keywords: adult XLH; burosumab; conventional therapy; efficacy; patient-important outcomes.