Background/aim: Burosumab is a monoclonal antibody against anti-FGF23, which has been recently approved for the treatment of X-linked hypophosphatemia (XLH). Beyond clinical trials, little is known about its efficacy/safety in clinical practice which is the aim of the present study.
Patients/methods: Thirty-nine children with XLH were switched from conventional therapy to burosumab (starting dose 0.4 mg/kg), on the basis of following indications: non-responder to conventional therapy (persistence of leg deformities, elevated levels of alkaline phosphatase, need for orthopaedic surgery, presence of neurological, dental, hearing complications, secondary hyperparathyroidism, height<-2SDS); intolerance to conventional therapy (nephrocalcinosis, hypercalciuria) or late diagnosis (>8 years). Serum phosphate level (sP) was checked before starting burosumab (M0) and monitored every 2 weeks for dose adjustment (target sP>1.2 mmol/l). Other parameters (weight, height, ALP, 1,25(OH)2D, PTH, TmP/eGFR, CaU/CrU, side effects) were checked at M0, thereafter at 3 and 6 months of treatment (M3-M6).
Results: Twenty-five girls/14 boys (mean age 9.6±3.8 years; 84.6% of subjects (n=33) with complications) were treated with conventional therapy for 7.7±3.8 years before starting burosumab. 26 patients completed 6 months of treatment. Upon burosumab, levels of sP, TmP/eGFR, 1,25(OH)2D increased significantly (sP 0.7±1.1→1.2±0.2→1.1±0.1 mmol/l; TmP/eGFR 0.6±1.1→1.1±0.2→1.0±0.2; 1,25(OH)2D 26.0±15.3→73.4±24.0→88.0±34.4 pg/ml at M0-M3-M6, respectively, p for trend=0.000) and ALP decreased (413±163→333±150 UI/l at M0-M6, respectively, P=0.3). However, PTH level and CaU/CrU ratio were not modified during the treatment. At M6, the average dose of burosumab was 1.3±0.5 mg/kg (45±23 mg); 61.5% (n=16) of patients did not achieve target sP level. At M6, 27% (n=7) of subjects received the maximal dose of burosumab (2.0 mg/kg or 90 mg), yet had low sP level. The number of complications was positively associated with the final dose of burosumab (32±13 vs 31±16 vs 57±24 mg for children with 0, ≤2 and >2 complications, respectively, P for trend=0.004). We did not observe severe adverse events during the treatment, the most frequent side effect being redness at sites of injection.
Conclusion: Treatment with burosumab restores phosphate reabsorption, increases sP and endogenous 1,25(OH)2D synthesis. The dose of burosumab needs to be increased with the severity of the disease.
18 May 2019 - 21 May 2019