To Örebro University

CONTEXT: Younger age at treatment-onset with conventional therapy (Pi/D) is associated with improved growth and skeletal outcomes in children with X-linked hypophosphatemia (XLH). The impact of age on burosumab efficacy and safety in XLH is unknown.

OBJECTIVE: Explore the efficacy and safety of burosumab versus Pi/D in younger (<5 years) and older (5 to 12 years) children with XLH.

DESIGN: Post-hoc analysis of 64-week, open-label, randomized controlled study.

SETTING: Sixteen academic centers.

PATIENTS OR OTHER PARTICIPANTS: Sixty-one children 1-12 years of age with XLH (younger, n=26; older, n=35).

INTERVENTIONS: 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).

MAIN OUTCOME MEASURE: 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 versus 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 (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.

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