Effect of Burosumab Compared With Conventional Therapy on Younger vs Older Children With X-linked Hypophosphatemia.

Abstract

CONTEXT:

Younger age at treatment onset with conventional therapy (phosphate salts and active vitamin D; Pi/D) is associated with improved growth and skeletal outcomes in children with X-linked hypophosphatemia (XLH). The effect of age on burosumab efficacy and safety in XLH is unknown.

OBJECTIVE:

This work aimed to explore the efficacy and safety of burosumab vs Pi/D in younger (< 5 years) and older (5-12 years) children with XLH.

METHODS:

This post hoc analysis of a 64-week, open-label, randomized controlled study took place at 16 academic centers. Sixty-one children aged 1 to 12 years with XLH (younger, n = 26; older, n = 35) participated. Children received burosumab starting at 0.8 mg/kg every 2 weeks (younger, n = 14; older, n = 15) or continued Pi/D individually titrated per recommended guidelines (younger, n = 12; older, n = 20). The main outcome measure included the least squares means difference (LSMD) in Radiographic Global Impression of Change (RGI-C) rickets total score from baseline to week 64.

RESULTS:

The LSMD in outcomes through 64 weeks on burosumab vs conventional therapy by age group were as follows: RGI-C rickets total score (younger, +0.90; older, +1.07), total Rickets Severity Score (younger, -0.86; older, -1.44), RGI-C lower limb deformity score (younger, +1.02; older, +0.91), recumbent length or standing height Z-score (younger, +0.20; older, +0.09), and serum alkaline phosphatase (ALP) (younger, -31.15% of upper normal limit [ULN]; older, -52.11% of ULN). On burosumab, dental abscesses were not reported in younger children but were in 53% of older children.

CONCLUSION:

Burosumab appears to improve outcomes both in younger and older children with XLH, including rickets, lower limb deformities, growth, and ALP, compared with Pi/D.

• Authors: Leanne M Ward, Francis H Glorieux, Michael P Whyte, Craig F Munns, Anthony A Portale, Wolfgang Högler, Jill H Simmons, Gary S Gottesman, Raja Padidela, Noriyuki Namba, Hae Il Cheong, Ola Nilsson, Meng Mao, Angel Chen, Alison Skrinar, Mary Scott Roberts, Erik A Imel
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 107 Issue 8 Pg. e3241-e3253 (07 14 2022) ISSN: 1945-7197 [Electronic] United States
• PMID: 35533340 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Fibroblast Growth Factors
• burosumab

Topics

• Adolescent
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Child
• Familial Hypophosphatemic Rickets (drug therapy)
• Fibroblast Growth Factors
• Humans
• Hypophosphatemia