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Effect of Burosumab Compared With Conventional Therapy on Younger vs Older Children With X-linked Hypophosphatemia
Leanne M Ward1, Francis H Glorieux2, Michael P Whyte3
1Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.
Insights
Burosumab effectively treats X-linked hypophosphatemia (XLH) in both younger and older children, improving rickets, growth, and bone health markers compared to conventional phosphate salts and active vitamin D (Pi/D) therapy.
Area of Science:
- Pediatric Endocrinology
- Skeletal Dysplasias
- Pharmacology
Background:
- X-linked hypophosphatemia (XLH) is a rare genetic disorder characterized by phosphate wasting and skeletal abnormalities.
- Early treatment with phosphate salts and active vitamin D (Pi/D) in children with XLH is linked to better growth and skeletal outcomes.
- The impact of patient age on the efficacy and safety of burosumab, a novel therapeutic agent for XLH, remains largely uncharacterized.
Purpose of the Study:
- To evaluate and compare the efficacy and safety of burosumab versus conventional Pi/D therapy in pediatric patients with XLH.
- To specifically analyze treatment effects stratified by age groups: younger children (under 5 years) and older children (5-12 years).
Main Methods:
- A post hoc analysis was conducted on data from a 64-week, open-label, randomized controlled study involving 61 children with XLH aged 1 to 12 years.
- Participants were divided into younger (n=26) and older (n=35) age cohorts.
- Children received either burosumab (0.8 mg/kg every 2 weeks) or continued individually titrated Pi/D therapy.
Main Results:
- Burosumab demonstrated improvements in rickets, lower limb deformity, growth (height Z-score), and serum alkaline phosphatase (ALP) levels across both younger and older age groups compared to Pi/D.
- Specific improvements included higher least squares means difference (LSMD) in RGI-C rickets total score (+0.90 younger, +1.07 older) and lower Rickets Severity Score (younger, -0.86; older, -1.44).
- While burosumab showed positive effects on growth and ALP, dental abscesses were reported in 53% of older children treated with burosumab, but not in younger children.
Conclusions:
- Burosumab exhibits therapeutic benefits for children with XLH, irrespective of age, in addressing key disease manifestations like rickets and impaired growth.
- The findings suggest burosumab is a viable treatment option, offering advantages over conventional Pi/D therapy in improving skeletal and biochemical parameters in pediatric XLH patients.
- Further investigation into the safety profile, particularly regarding dental adverse events in older children, is warranted.
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.
