ESPE Abstracts

Background: X-linked hypophosphataemic rickets (XLH) is a genetic disorder, characterized by hypophosphatemia and caused by a mutation in the phosphate regulating endopeptidase homolog, X-linked (PHEX) gene which leads to overexpression of fibroblast growth factor 23 (FGF23).^1,2 Conventional therapy, supplementation with oral phosphate and vitamin D analogs, does not treat the underlying cause of the disorder and is associated with poor treatment adherence, high rate of failure and long-term side effects.³ Burosumab, a human monoclonal anti FGF23 antibody, has been shown to alleviate symptoms of XLH by addressing the underlying pathophysiology of the disease.⁴ This study aimed to assess the effect of 6-months of burosumab treatment in XLH patients from a Kuwaiti family.

Methods: This prospective observational study collected clinical and biochemical parameters (fasting serum phosphate [ mmol/l], tubular maximum reabsorption of phosphate to glomerular filtration rate [TmP/GFR; mmol/l], serum calcium [ mmol/l], alkaline phosphatase [ALP; IU/L] and active vitamin D [nmol/l]) for 5 XLH patients at baseline (prior to burosumab treatment) and every 4 weeks during the first 6-months of treatment. X-rays were also performed at baseline and at 6-months. Burosumab was initiated at a starting dose of 0.8 mg/kg for the three pediatric patients and 1 mg/kg for the two adult patients, following a washout period of one week after cessation of conventional therapy.

Results: All patients were female, aged 2‒5 years at diagnosis and 7‒20 years at burosumab initiation. All patients experienced increased serum phosphate (mean change versus baseline +0.23 mmol/l) following 6-months of burosumab treatment, with three patients achieving levels within the normal range. All patients also had reduced ALP (mean -81.40 IU/L) and increased TmP/GFR (mean +0.06 mmol/l) following 6-months of burosumab treatment. X-rays showed improvements in rickets. Patients also reported improvements in their quality of life - having more active mobility and experiencing less bone pain as well as being free of daily medications. No adverse events were reported with burosumab treatment.

Conclusions: Six-months of burosumab treatment led to improvements in clinical and biochemical parameters in these five XLH siblings from the State of Kuwait.

References: 1. Sako S, et al. Hum Genome Var. 2019;6: 9. 2. Linglart A, et al. Endocr Connect. 2014;3(1): R13-30. 3. Skrinar A, et al. J Endocr Soc. 2019;3(7): 1321-34. 4. Carpenter TO, et al. N Engl J Med. 2018;378(21): 1987-98.