Burosumab prevents further height deficit in toddlers affected by XLH.

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 4 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 1 and 4 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 4 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 4 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 years (range: 1-2.9 years). 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 2 years of treatment: mean ± SD 0.1 ± 0.6 (range: -0.7-1.3 SDS) after 1 year (P = 0.16) and 0.0 ± 0.7 SD (range: -0.6-1.4 SDS) after 2 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 2 years of therapy when compared to birth length SDS (P = 0.04). BMI SDS did not significantly change during the first 2 years on burosumab. Children treated with vitamin D analogs and phosphate supplements started treatment at a mean ± SD age of 1.3 ± 0.7 years (range: 0.1-3.0 years) and presented a continuous decline in height SDS of 0.7 ± 0.9 SDS (range: -2.6-1) during the first 2 years of therapy (P < 0.001) and up to 4 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). Conclusion: We present data from the largest pediatric XLH cohort of very young children treated with burosumab over a follow-up period of 2 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 high growth velocity. In addition, burosumab prevents the early and excessive weight gain associated with the development of XLH in children. Significance statement: Most patients with X-linked hypophosphatemic rickets (XLH) present with short stature. This is the first large study on XLH children younger than 5 years treated with burosumab since a mean age of 2.1 years. We analyzed growth over a period of 2 years of therapy. Our data show that, in XLH toddlers, burosumab therapy prevents the further loss of height and the weight gain observed in patients treated with oral phosphate and active vitamin D therapy at the same age. As burosumab leads to better long-term outcomes in these children, we hope that our work will encourage the early use of burosumab and motivate further research in this field.