medwireNews: Children with X-linked hypophosphatemia derive similar benefits from burosumab regardless of whether they start treatment before or after the age of 5 years, shows a post-hoc analysis of a randomised trial.
The researchers explain that randomisation for the trial was stratified by age of younger than 5 years or older, “to ensure even age distribution between treatment arms”, allowing a post-hoc analysis by age category.
Of the 61 children in the trial, 26 were younger than 5 years. Those randomly assigned to take burosumab received it as a subcutaneous injection every 2 weeks, starting at a dose of 0.8 mg/kg.
The dose was increased to 1.2 mg/kg in eight children who had low serum phosphorus, but the average dose remained similar between the age groups, at an average of 0.80 and 0.81 mg/kg in the younger and older children, respectively.
The primary endpoint was rickets severity, assessed as the average Radiographic Global Impression of Change (RGI-C) rickets total score. At week 40, this averaged 2.04 in younger children and 2.06 in older children taking burosumab, compared with 1.14 and 0.99, respectively, in those taking conventional therapy (phosphate salts and vitamin D).
In addition, the average total rickets severity score improved by 2.26 and 2.20 points in the younger and older children taking burosumab, respectively, and at week 64, RGI-C lower limb deformity scores were similar irrespective of age, at a corresponding 1.48 and 1.02.
None of the differences in outcomes between children in the younger and older age categories were statistically significant, stress Leanne Ward (University of Ottawa, Ontario, Canada) and co-researchers in The Journal of Clinical Endocrinology & Metabolism.
The improvements in measures of rickets in children taking burosumab were paralleled by improvements in phosphate homeostasis, with significant and sustained increases in fasting serum phosphorus and the tubular maximum for phosphate reabsorption per glomerular filtration rate. Again, the improvements were similar in both age categories.
Both age groups also showed improved growth while taking burosumab, with the length or height standard deviation score increasing by an average of 0.15 and 0.17 by week 64 in the younger and older children, respectively, from a baseline of –2.27 and –2.36.
Although age did not appear to impact the effect of burosumab on growth outcomes, the researchers say that a larger sample size would be needed “to address this issue more definitively.”
But noting the minimum age of 1 year in their trial, they add: “Ideally, such a study would also include infants who manifested renal [phosphate] wasting and signs of rickets, since linear growth is rapid during the first year of life, and therefore, the first year may be a particularly sensitive time for optimization of growth plate mineralization.”
By Eleanor McDermid
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