Oral Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Burosumab in adults with X-linked hypophosphatemia: real-world experience from a retrospective study in Sydney  (#208)

Shejil Kumar 1 2 3 , Christian M Girgis 3 4 , Brian Tran 3 , Malu (Luzviminda) Alvarez 1 , Roderick J Clifton-Bligh 1 2
  1. Endocrinology Department, Royal North Shore Hospital, Sydney
  2. Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
  3. Endocrinology Department, Westmead Hospital, Sydney
  4. Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia

Aims: X-linked hypophosphatemia (XLH) is a chronic disabling hereditary musculoskeletal disorder associated with elevated circulating FGF-23 concentrations. In a placebo-controlled trial of adults with XLH, burosumab (anti-FGF-23 antibody) demonstrated durable improvements in phosphate concentrations, and self-reported stiffness and physical limitation. However, real-world data is lacking regarding burosumab efficacy and tolerability in adults with XLH.

Methods: A retrospective audit was performed of patients (age ≥18-years) who commenced four-weekly subcutaneous burosumab for XLH at Royal North Shore and Westmead Hospitals, Sydney, from January 2021-June 2024. Patients were managed per standard clinical care and burosumab dose adjusted as necessary according to manufacturer instructions. Electronic medical records were reviewed to collate data regarding patient demographics, XLH-related complications and prior treatment, burosumab dosage and side effects, and pre- and post-burosumab biochemistry and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores.

Results: Of thirteen adults with XLH, all had hypophosphatemia before commencing burosumab (mean 0.64±0.08 mmol/L). Mean WOMAC scores demonstrated baseline impairments in stiffness, pain and physical limitation. Burosumab was administered for median 15 months during follow-up (median dose 70 mg). Hypophosphatemia resolved in all patients within three months of burosumab (mean 1.03±0.38 mmol/L). Two patients developed hyperphosphatemia two weeks after commencing burosumab requiring dose reduction. One patient ceased burosumab in the setting of hypercalcaemia and constipation secondary to pre-existing tertiary hyperparathyroidism. Adverse events were mild, including transient musculoskeletal discomfort (n=4), restless legs (n=2), injection site reaction (n=2) and headache (n=1). Repeat WOMAC within 12 months of commencing burosumab (n=9) demonstrated clinically meaningful improvements in stiffness (33.3±12.5%, p<0.001) and physical function (14.3±16.2%, p=0.029).

Conclusion: This study reports real-world outcomes of adults with XLH treated with burosumab. Clinical experience from two centres in Sydney support trial findings that burosumab is well-tolerated and associated with improved serum phosphate concentrations and self-reported stiffness and physical function.

 

66b82f9d70bbc-XLH+burosumab+fig1+(1).png

  1. Ariceta G, Beck-Nielsen SS, Boot AM, et al. The International X-linked Hypophosphatemia (XLH) Registry: first interim analysis of baseline demographic, genetic and clinical data. Orphanet J Rare Dis. 2023;18(1):304.
  2. Portale AA, Carpenter TO, Brandi ML, et al. Continued beneficial effects of burosumab in adults with X-linked hypophosphatemia: results from a 24-week treatment continuation period after a 24-week double-blind placebo-controlled period. Calcif Tissue Int. 2019;105:271-284.
  3. Arcidiacono T, Foligno NE, Brioni E, et al. Different Efficacy of Burosumab on Physical Performance and Serum Phosphate in Adult Patients with X-Linked Hyphophosphatemic Rickets during the First Six-Month of Treatment. J Clin Med. 2023;12(8):2906. doi: 10.3390/jcm12082906.
  4. Vaisbich MH, de Cillo ACP, Silva BCC, et al. Real-world data of Brazilian adults with X-linked hypophosphatemia (XLH) treated with burosumab and comparison with other worldwide cohorts. Mol Genet Genomic Med. 2024;12(2):e2387. doi: 10.1002/mgg3.2387.
  5. Skrinar A, Theodore-Oklota C, Bonner N, et al. Confirmatory psychometric validation of the Western Ontario McMaster Universities Osteoarthritis Inventory (WOMAC) in adult X-linked hypophosphataemia (XLH). 2019. Program of ISPOR Europe 2019, Copenhagen, Denmark (Abstract PRO152).