Sex differences of burosumab in children with X-linked hypophosphataemic rickets.

Abstract

The severity of X-linked hypophosphataemic rickets (XLH) may be affected by genotype and sex. However, burosumab, a fully humanized monoclonal antibody against fibroblast growth factor 23, has the same pediatric dose recommendation for both sexes (0.8mg/kg every 2weeks). In a retrospective cohort study, we describe the burosumab response differences by sex in children with XLH. We treated 10 children (5 females, mean age at initiation 4.2 ± 3.5years) with XLH with burosumab. Initial mean serum phosphate was 0.69 ± 0.18mmol/L in males and 0.86 ± 0.22mmol/L in females (p = 0.108). The mean ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) was 0.55 ± 0.11mmol/L in males and 0.76 ± 0.23mmol/L in females (p = 0.06). The mean starting dose of burosumab was 0.83 ± 0.19mg/kg subcutaneously every 14days (males: 0.79 ± 0.19mg/kg; females: 0.87 ± 0.21mg/kg, n.s.). Two weeks after starting burosumab, serum phosphate differed significantly between males (0.90 ± 0.21mmol/L) and females (1.27 ± 0.25mmol/L) (p = 0.018). All males required a dose increase to try to normalize serum phosphate. On day 140 after starting, the average dose in males increased further to 1.24 ± 0.41mg/kg to achieve a phosphate of 0.87 ± 0.11mmol/L while females had a normal phosphate and alkaline phosphatase on the starting dose. After a mean of 458 ± 79days, the mean burosumab dose/kg in males was 1.68 ± 0.61mg/kg, mean serum phosphate was 1.08 ± 0.23mmol/L, mean TmP/GFR was 1.01 ± 0.20, mean alkaline phosphatase had normalized to 303.6 ± 40.7U/L, and mean 1.25(OH)2 vitamin D level was 186.4 ± 16.6nmol/L. Our findings may suggest a sex difference in response to burosumab in XLH patients. Our data suggest that males may require higher doses.