Endocrine Abstracts

Background: Burosumab (a monoclonal antibody inhibiting elevated FGF23 activity) targets the pathophysiology of XLH better than conventional phosphate and activated Vitamin D and shows encouraging research findings. Whilst marketing authorisation underway, enrolment into a Named Patient Scheme was possible. Delivery of new treatment modalities can present practical challenges. We report our experience of initiating the first UK cohort.

Methods: Seven patients (2M:5F), median age 8.3 (range 2.6–12.1) years met inclusion criteria of physical or radiological evidence of bone disease despite conventional treatment, aged >1year and incomplete linear growth. XLH diagnosed median age 4.2 years, all had confirmed PHEX mutation (n=6 and n=1 in family member). We developed a fortnightly cohorted nurse-led clinic; processes included clear SOP documentation, patient treatment card and monitoring proforma. Conventional medications were stopped 7 days ahead. Fortnightly Burosumab subcutaneously commenced 0.4 mg/kg, venepuncture performed visits 1,2,3,5,7, dose increments of 0.4 mg/kg at monthly intervals until serum phosphate levels normalised. Quality of Life measure EQ-5D-Y administered at baseline and visit 7.

Results: Normophosphataemia achieved in all within 3 months: two patients normophosphataemic by 1 month, 5 patients required dose increase to 0.8 mg/kg at Visit 3, of which two needed further dose increments. No hyperphosphataemia occurred. ALP improved in 6/7 patients (median reduction 103IU/l). Burosumab injection well tolerated, 5 reported mild side effects: injection site reaction (n=1), short duration dizziness ± headaches/malaise (n=4). Mean EQ-5D-Y score improved from 60 at baseline to 92.0 at 3 months (n=6). Maintenance doses on transfer to homecare administration at 3 months were 0.4 mg/kg (n=2), 0.8 mg/kg (n=3), 1.2 mg/kg (n=1) and 1.6mg/kg (n=1) fortnightly.

Conclusion: Burosumab was successful in promptly normalising phosphate and reducing ALP. Implementing this new therapy with a cohorted approach, improved consistency of monitoring, dose optimisation, side effects monitoring and was healthcare resource efficient, although did increase patient travel burden for this initiation. Concordance with treatment was good and well tolerated. The cohorted approach also facilitated social interaction between affected families with this rare bone disease with the emergence of an ongoing informal patient support network.