TY - JOUR
T1 - Burosumab vs Phosphate/Active Vitamin D in Pediatric X-Linked Hypophosphatemia
T2 - A Subgroup Analysis by Dose Level
AU - Imel, Erik A.
AU - Glorieux, Francis H.
AU - Whyte, Michael P.
AU - Portale, Anthony A.
AU - Munns, Craig F.
AU - Nilsson, Ola
AU - Simmons, Jill H.
AU - Padidela, Raja
AU - Namba, Noriyuki
AU - Cheong, Hae Il
AU - Pitukcheewanont, Pisit
AU - Sochett, Etienne
AU - Högler, Wolfgang
AU - Muroya, Koji
AU - Tanaka, Hiroyuki
AU - Gottesman, Gary S.
AU - Biggin, Andrew
AU - Perwad, Farzana
AU - Chen, Angel
AU - Roberts, Mary Scott
AU - Ward, Leanne M.
N1 - Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - 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.
AB - 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.
KW - FGF23
KW - X-linked hypophosphatemia
KW - XLH
KW - active vitamin D
KW - burosumab
KW - oral phosphate
KW - rickets
UR - http://www.scopus.com/inward/record.url?scp=85175118781&partnerID=8YFLogxK
U2 - 10.1210/clinem/dgad230
DO - 10.1210/clinem/dgad230
M3 - Article
C2 - 37084401
AN - SCOPUS:85175118781
SN - 0021-972X
VL - 108
SP - 2990
EP - 2998
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
ER -