Burosumab, a monoclonal antibody targeting fibroblast growth factor 23, is now available for clinical use in children with X-linked hypophosphatemia (XLH). We explored the effects of this treatment in a clinical setting, considering biochemistry, growth, deformity, functionality, quality of life, pain and fatigue.
Methods: Clinical, biochemical, radiological and questionnaire data were reviewed at 6 and 12 months in a cohort of 8 children with XLH starting burosumab. Functionality was assessed with 6-minute walk test (6MWT) and Timed Up and GO (TUGLndon). Questionnaires included: Core Paediatric Quality of Life Inventory (PedsQL-Core), Paediatric Quality of Life multidimensional fatigue scale (PedsQL-Fatigue), and Brief Pain Index Pain Severity Score (PSS).
Results: Median age was 5.5 years (range=19 months-11 years). Table below shows radiological, biochemical and functional improvements over 12 months.
|Test (Normal range)||Baseline Mean±SD||12 month Mean±SD||P value (Paired t-test)|
|Ur Ca:Creatinine(0.05-0.60)||0.44±0.21||0.37±0.23||Not significant,P=0.51|
|Thatcher Scores (out of 10)||2.0±1.5||0.4±0.3||P<0.05|
|*Alkaline Phosphatase, **Parathyroid hormone, ***Calculated ratio of renal tubular maximum phosphate reabsorption ****63-183metres below age/gender-matched norms|
Deformity: Six children had lower limb deformity; varus(N=3), valgus(N=2), windswept(N=1). The most severely affected patient (intermalleolar distance=10cm) noted progression at 6 months with slight improvement by 12 months. All others noticed improvement at 12 months with reduced intercondylar/intermalleolar distances.
Pain/Fatigue: One child reported no pain. 12 month PSS decreased for 6 patients and slightly increased for one. Mean±SD PSS was 2.3±1.3 at baseline and 1.0±1.2 at 12 months (maximum score 10). Mean±SD PEDsQL-Fatigue scores were 64±19 at baseline and 76±17 at 12 months (maximum score 100,P=0.2).
Quality of Life: Mean±SD PEDsQL-Core score improved from 69±17 at baseline to 81±15 at 9 months, however decreased back to 67±17 by 12 months (N=7,maximum score 100). This is despite verbal reports of improvements and may reflect a shift in expectation.
Conclusion: In a real-world setting, burosumab can improve biochemistry, growth, deformity, pain and function in children with XLH
19 - 21 Sep 2019
European Society for Paediatric Endocrinology