ESPE Abstracts

XLH is the commonest inherited form of rickets. Impaired regulation of fibroblast growth factor 23 (FGF23) due to PHEX gene mutation leads to reduced tubular reabsorption of phosphate (TmP/GFR) and 1,25-dihydroxyvitamin D (1,25(OH)2D) synthesis with hypophosphatemia. Patients show rickets and osteomalacia, bone and muscular pain, stunted growth, and reduced quality of life. We report preliminary data on burosumab therapy in a selected sample of Italian patients.

Patients and Methods: We enrolled 15 patients with XLH confirmed by PHEX gene mutation (age 11.1±4.3 yr; 8 M, 7 F) receiving conventional treatment (inorganic oral phosphate salts and calcitriol or alphacalcidol) from 8.2±4.3 yr. Conventional treatment was stopped for 7-10 days and then burosumab (Crysvita, Kyowa-Kirin, Japan) was started (at entry 0.4-0.8 mg/kg/d; maintenance 1.2-1.4 mg/kg/d, s.c. every two weeks). In all patients serum phosphate and TmP/GFR were measured at baseline and after 6 and 12 months of burosumab. In all patients intact FGF23 plasma levels (DiaSorin, Liaison, Saluggia, Italy) and serum 1,25(OH)2D levels (RIA, IDS, UK) were measured at entry, too. In growing patients (n=10) rickets severity score (RSS, Thacher TD, 2019) was assessed at baseline and after 12 months. In adolescents (n=5) approaching growth cessation and epiphyseal fusion Womac score was assessed at baseline and after 6 months of burosumab.

Results: At entry, all patients had hypophosphatemia (2.1±0.4 mg/dL) and reduced TmP/GFR (1.7±0.5 mg/dL). After 6 months: serum phosphate 3.3±0.4 mg/dl, D57%, P<0.0001; TmP/GFR 2.9±0.5 mg/dl, D71%, P<0.0001. After 12 months: serum phosphate 3.0±0.5 mg/dl, D43%, P<0.0001; TmP/GFR 2.6±0.5 mg/dl, D53%, P<0.0001. Mean intact FGF23 plasma levels and serum 1,25(OH)2D levels was 122.4±74 ng/ml (in all patients >40 ng/mL) and 27.4±7.7 pg/ml (nv 20-120 pg/mL), respectively. RSS and Womac score improved significantly (5.9±1.6 to 2.6±0.8, P<0.0001) and (71.2±8.1% to 34.8±5.6%, P<0.0001), respectively. Injection-site reaction was reported in one patient. No other adverse effect was observed.

Comments: After transition to burosumab the improvement of serum phosphate and RSS was greater than that observed during the conventional therapy. Biochemical effect on serum phosphate and TmP/GFR was maintained after 12 months of burosumab treatment. RSS and Womac score were effective to assess bone health in children and adolescents with XLH receiving burosumab treatment, respectively.