Burosumab vs Phosphate/Active Vitamin D in Pediatric X-Linked Hypophosphatemia: A Subgroup Analysis by Dose Level

Erik A. Imel, Francis H. Glorieux, Michael P. Whyte, Anthony A. Portale, Craig F. Munns, Ola Nilsson, Jill H. Simmons, Raja Padidela, Noriyuki Namba, Hae Il Cheong, Pisit Pitukcheewanont, Etienne Sochett, Wolfgang Högler, Koji Muroya, Hiroyuki Tanaka, Gary S. Gottesman, Andrew Biggin, Farzana Perwad, Angel Chen, Mary Scott RobertsLeanne M. Ward

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

CONTEXT: In an open-label, randomized, controlled, phase 3 trial in 61 children aged 1 to 12 years with X-linked hypophosphatemia (XLH), burosumab improved rickets vs continuing conventional therapy with active vitamin D and phosphate. OBJECTIVE: We conducted an analysis to determine whether skeletal responses differed when switching to burosumab vs continuing higher or lower doses of conventional therapy. METHODS: Conventional therapy dose groups were defined as higher-dose phosphate [greater than 40 mg/kg] (HPi), lower-dose phosphate [40 mg/kg or less] (LPi), higher-dose alfacalcidol [greater than 60 ng/kg] or calcitriol [greater than 30 ng/kg] (HD), and lower-dose alfacalcidol [60 ng/kg or less] or calcitriol [30 ng/kg or less] (LD). RESULTS: At week 64, the Radiographic Global Impression of Change (RGI-C) for rickets was higher (better) in children randomly assigned to burosumab vs conventional therapy for all prebaseline dose groups: HPi (+1.72 vs +0.67), LPi (+2.14 vs +1.08), HD (+1.90 vs +0.94), LD (+2.11 vs +1.06). At week 64, the RGI-C for rickets was also higher in children randomly assigned to burosumab (+2.06) vs conventional therapy for all on-study dose groups: HPi (+1.03), LPi (+1.05), HD (+1.45), LD (+0.72). Serum alkaline phosphatase (ALP) also decreased in the burosumab-treated patients more than in the conventional therapy group, regardless of on-study phosphate and active vitamin D doses. CONCLUSION: Prior phosphate or active vitamin D doses did not influence treatment response after switching to burosumab among children with XLH and active radiographic rickets. Switching from conventional therapy to burosumab improved rickets and serum ALP more than continuing either higher or lower doses of phosphate or active vitamin D.

Original languageEnglish
Pages (from-to)2990-2998
Number of pages9
JournalThe Journal of clinical endocrinology and metabolism
Volume108
Issue number11
DOIs
StatePublished - Oct 18 2023

Keywords

  • FGF23
  • X-linked hypophosphatemia
  • XLH
  • active vitamin D
  • burosumab
  • oral phosphate
  • rickets

Fingerprint

Dive into the research topics of 'Burosumab vs Phosphate/Active Vitamin D in Pediatric X-Linked Hypophosphatemia: A Subgroup Analysis by Dose Level'. Together they form a unique fingerprint.

Cite this