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

• Published in: The journal of clinical endocrinology and metabolism Vol. 107; no. 8; pp. e3241 - e3253
• Main Authors: Ward, Leanne M, Glorieux, Francis H, Whyte, Michael P, Munns, Craig F, Portale, Anthony A, Hogler, Wolfgang, Simmons, Jill H, Gottesman, Gary S, Padidela, Raja, Namba, Noriyuki, Cheong, Hae Il, Nilsson, Ola, Mao, Meng, Chen, Angel, Skrinar, Alison, Roberts, Mary Scott, Imel, Erik A
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.08.2022
• Subjects: Abscess; Alfacalcidol; burosumab; Calcifediol; children; Comparative analysis; fibroblast growth factor 23; Fibroblast growth factors; Hypophosphatemia; Medicin och hälsovetenskap; Online Only; Patient compliance; Phosphatases; Phosphates; rickets; Vitamin D; X-linked hypophosphatemia; Canada
• DOI: 10.1210/clinem/dgac296
• ISSN: 0021-972X; 1945-7197

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.