Burosumab in the management of X-linked hypophosphataemia: a retrospective cohort study reviewing anthropometric and biochemical markers

Abstract Introduction Rickets is a bone disease caused by a defect in mineralization. When left untreated, it has lifelong Orthopaedic sequelae. Burosumab, an anti-fibroblast growth factor 23 monoclonal antibody, improves rickets severity, symptoms, and growth in children with X-linked hypophosphataemia (XLH) followed to 64 weeks in clinical trials. International dosing guidance recommends targeting normal serum phosphate concentration. However, some children may not achieve this despite maximal dosing. This study compares clinical outcomes in children with XLH on long-term burosumab treatment who achieved normal phosphate, vs those who did not. Methods Single-centre retrospective review of a large paediatric cohort with XLH treated with burosumab. We evaluated growth and biochemical markers of bone health in those who did compared to those who did not achieve normal plasma phosphate concentration. Results Fifty-five children with XLH with median age 11.7 [6.8–15.5] years were included. 27 (49%) had low plasma phosphate concentration, and 27 (49%) normal phosphate after a median burosumab treatment duration of 3.3 [IQR 2.6–3.7] years. 1 (2%) did not have a recent phosphate level recorded. No difference in growth was found between normal and abnormal phosphate groups (p = 0.9). A trend of superior growth in those with normal compared with abnormal alkaline phosphatase level was observed. Conclusion Young children with XLH experience sustained growth on long-term burosumab treatment, albeit without normal plasma phosphate concentration in many. Consideration should be made to changing burosumab dosing recommendations to target the normalisation of alkaline phosphatase instead of plasma phosphate concentration.