BUROSUMAB PREVENTS FURTHER HEIGHT DEFICIT IN TODDLERS AFFECTED BY XLH.

Abstract

Background: X-linked hypophosphatemia (XLH) is a rare disease caused by PHEX variants. Besides rickets, XLH leads to disproportionately short stature which develops during the first months of life. Burosumab afforded minimal improvement of growth in children above the age of four years. No data are available on growth, including body mass index, of XLH children who started burosumab at a very young age, i.e., between one and four years.

Methods: We performed a prospective follow-up of growth and other XLH-related outcomes in XLH children who started burosumab before the age of four years. We compared these children 1:2 with a historical cohort of XLH children who started vitamin D analogs and phosphate supplements before the age of four years.

Results: We included 15 children treated with burosumab and 31 children treated with vitamin D analogs and phosphate supplements. In the burosumab-treated group, mean± SD for age at therapy baseline was 2.1± 0.7 (range: 1-2.9 years old). They were treated with oral phosphate and active vitamin D for 1.7±0.8 years before switching to burosumab. From birth to burosumab start, they presented a decline in height standard deviation score (SDS) from -0.3±0.7 to -1.4±0.8 (mean± SD), respectively, p<0.001. On burosumab, height SDS did not decline further during the first two years of treatment: mean± SD 0.1±0.6 (range: -0.7- 1.3 SDS) after one year (p=0.16) and 0.0±0.7 SD (range: -0.6- 1.4 SDS) after two years (p=0.54). Burosumab did not correct the acquired height deficit as children had a difference in height SDS of -1.5 SDS after two years of therapy when compared to birth length SDS (p=0.04). BMI SDS did not significantly change during the first two years on burosumab. Children treated with vitamin D analogs and phosphate supplements started treatment at a mean± SD age of 1.3±0.7 (range: 0.1-3.0 years old) and presented a continuous decline in height SDS of 0.7±0.9 SDS (range: -2.6- 1) during the first two years of therapy (p<0.001) and up to four years of age (-1.8 ± 0.9 SDS, to -1.9 ± 0.9, respectively). BMI SDS increased by 0.5±0.9 SDS (range: -0.6- 1.9) during the same period (p=0.006).

In conclusion: we present data from the largest pediatric XLH cohort of very young children treated with burosumab over a follow-up period of two years. Our data suggest that, in contrast to the combination of vitamin D analogs and phosphate supplements, burosumab prevents further height deficit in XLH children, even at a period of life associated with a high growth velocity. In addition, burosumab prevents the early and excessive weight gain associated with the development of XLH in children.