Background/Aim: X-linked hypophosphatemia (XLH) is a rare disease caused by mutations in PHEX, leading to elevated FGF23 levels, hypophosphatemia and chronic renal phosphate wasting. Burosumab is a monoclonal antibody against anti-FGF23, which has been recently approved for treatment of XLH. Beyond clinical trials, little is known about its efficacy/safety in clinical practice which is the aim of study.
Patients/Methods: 45 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 and elevated levels of alkaline phosphatase, need for orthopaedic surgery, presence of neurological, dental, hearing complications, secondary hyperparathyroidism, height<-2SDS treated or not with rhGH); intolerance to conventional therapy (nephrocalcinosis), 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 (ALP, 1,25(OH)2D, PTH, TmP/eGFR, CaU/CrU, side effects) were checked at M0, thereafter at 3-6-9 months of treatment (M3-M6-M9). Severe and non-severe forms of XLH were defined by >2 and ≤2 complications.
Results: 45 children (29 girls/16 boys, mean age 9.7±3.7 years) were treated with conventional therapy for 7.3±3.9 years before starting burosumab. 28 patients completed 9 months of burosumab treatment. Upon burosumab, levels of sP, TmP/eGFR, 1,25(OH)2D increased significantly (sP 0.7±0.1→1.2±0.2→1.2±0.2→1.2±0.1 mmol/l; TmP/eGFR 0.6±1.1→1.1±0.2→1.1±0.2→1.1±0.1;1,25(OH)2D26.2±15.7→73.8±22.7→88.4±39.9→82.5±19.9 pg/ml, M0-M3-M6-M9, respectively, p for trend=0.000) and ALP decreased significantly(414±153→339±141→339±146→313±148UI/l, M0-M3-M6-M9, respectively, p for trend=0.036). At M9, the average dose of burosumab was 1.4±0.5 mg/kg (47±25 mg); 39% (n=9) of patients did not achieve target sP level. At M9, 32% (n=9) of subjects received the maximal dose of burosumab (2.0 mg/kg or 90 mg), yet having low sP level. Children with the severe form of XLH needed higher final dose of burosumab compared with patients having the non-severe form (1.4±0.5 vs 1.1±0.5 mg/kg, 53±27 vs 34±20 mg, respectively, P=0.068 and 0.017, respectively). No severe adverse events were noticed, the most frequent side effect being redness at sites of injection, muscular/bone/abdominal pain.
Conclusion: Treatment with burosumab restores phosphate renal reabsorption, increases sP and endogenous 1,25(OH)2D synthesis. The dose of burosumab should be adjusted to the severity of the disease.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology