ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 66 P8 | DOI: 10.1530/endoabs.66.P8

Clinical, functional and quality of life outcomes of Burosumab therapy in children with X-linked hypophosphoataemia: a real world, London experience

Jessica Sandy, Robyn Gilbey-Cross, Rui Santos, Sophia Sakka, Alessandra Cocca, Mavali Morris, Jill Massey & Moira Cheung

Evelina London Children’s Hospital, London, UK

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=19m–11y). 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.

TestBaseline Mean±S.D.12m Mean±S.D.P value
Phosphate (1.0–1.9 mmol/l)0.7±0.11.1±0.1P<0.001
ALP* (139–347 IU/l) 415±73322±70P<0.001
PTH** (10–65 ng/l)31±1442±16P<0.05
Ur Ca:Creatinine (0.05–0.60)0.44±0.210.37±0.23Not significant, P=0.51
TmP/GFR1 *** (1.15–2.44)0.56±0.111.19±0.18P<0.001
Height Z-scores−2.600±0.813−2.435±0.787P<0.05
Thatcher Scores (out of 10)2.0±1.50.4±0.3P<0.05
TUG (N=5,seconds)5.7±0.54.8±0.6P<0.05
6MWT (N=4, metres)258±75447±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.