Burosumab, 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(m) for 8 children with XLH starting burosumab as well as 6-minute walk test (6MWT) and Timed Up and GO (TUG). Questionnaires included: Core Paediatric Quality of Life Inventory (PedsQL-Core), PedsQL multidimensional fatigue scale (PedsQL-Fatigue), and Brief Pain Index Pain Severity Score (PSS).
Results: Median age was 5.5 years(y) (range=19m11y). Table below shows clinical and functional improvements over 12m.
Deformity: Six children had lower limb deformity; varus(N=3), valgus(N=2), windswept(N=1). All but one noticed improvement at 12m with reduced intercondylar/intermalleolar distances.
Pain/fatigue: One child reported no pain. 12m PSS scores decreased for 6 patients and increased for 1. 3 recorded higher PSS at 6m, improving by 12m. PSS Mean±S.D. was 2.3±1.3 at baseline and 1.0±1.2 at 12m (maximum score 10). Mean±S.D. PEDsQL-Fatigue scores were 64±19 at baseline and 76±17 at 12m (maximum score 100, P=0.2).
Quality of Life: Mean±S.D. PEDsQL-Core score improved from 69±17 at baseline to 81±15 at 9m, however decreased to 67±17 by 12m (N=7,maximum score 100). This is despite verbal reports of improvements and may reflect a shift in expectation.
|Test||Baseline Mean±S.D.||12m Mean±S.D.||P value|
|Phosphate (1.01.9 mmol/l)||0.7±0.1||1.1±0.1||P<0.001|
|ALP* (139347 IU/l)||415±73||322±70||P<0.001|
|PTH** (1065 ng/l)||31±14||42±16||P<0.05|
|Ur Ca:Creatinine (0.050.60)||0.44±0.21||0.37±0.23||Not significant, P=0.51|
|TmP/GFR1 *** (1.152.44)||0.56±0.11||1.19±0.18||P<0.001|
|Thatcher Scores (out of 10)||2.0±1.5||0.4±0.3||P<0.05|
|6MWT (N=4, metres)||258±75||447±53****||P=0.05|
|*Alkaline Phosphatase, **Parathyroid hormone, ***Ratio of renal tubular maximum phosphate reabsorption.|
Conclusion: In a real-world setting, burosumab can improve biochemistry, growth, deformity, pain and function in children with XLH.
27 - 29 Nov 2019
British Society for Paediatric Endocrinology and Diabetes