ICCBH2019 Poster Presentations (1) (226 abstracts)
Higher dose of burosumab is needed for treatment of children with severe forms of X-linked hypophosphatemia
Volha V Zhukouskaya 1, , Christelle Audrain 1 , Anne-Sophie Lambert 1, , Annamaria Colao 2 , Peter Kamenicky 1, , Catherine Adamsbaum 1, , Jerome Nevoux 1, , Catherine Chaussain 1, , Philippe Wicart 1, , Karine Briot 1, , Federico Di Rocco 1, , Séverine Trabado 3, , Dominique Prié 15, , Anya Rothenbuhler 1, & Agnès Linglart 1,
1APHP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filiere OSCAR and Platform of Expertise for Rare Diseases Paris-Sud, Bicêtre Paris-Sud Hospital, Le Kremline Bicetre, France; 2Department of Clinical Medicine and Surgery, Division of Endocrinology, University of Naples Federico II, Naples, Italy; 3Paris Sud – Paris Saclay University, Faculté de Médecine, Le Kremlin- Bicêtre, France; 4APHP, Department of Endocrinology and Diabetology for children, Bicêtre Paris Sud Hospital, Le Kremlin- Bicêtre, France; 5APHP, Department of Endocrinology and Reproductive Diseases, Bicêtre Paris Sud Hospital, Le Kremlin- Bicêtre, France; 6APHP Department of Pediatric Radiology, Bicêtre Paris Sud Hospital, Le Kremlin- Bicêtre, France; 7APHP Department of ORL, Bicêtre Paris Sud Hospital, Le Kremlin- Bicêtre, France; 8Department of Odontology-Maladies Rares, Hospital Bretonneau, Paris, France; 9Université Paris Descartes, Paris, France; 10Department of Pediatric orthopaedic surgery, Necker - Sick Kids University Hospital, Paris, France; 11APHP, Department of Rheumatology Hospital Cochin, Paris, France; 12Pediatric Neurosurgery, Hospital Femme Mere Enfant, Hospices Civiles de Lyon and University Claude Bernard Lyon, Bron Cedex, France; 13Reference Center for Craniosynostosis, INSERM 1033, Lyon, France; 14APHP, Department of Molecular Genetics, Pharmacogenetics and Hormonology, Bice^tre Paris-Sud Hospital, Le Kremlin Bicêtre, France; 15Université Paris V, Faculté de Médecine, Paris, France; 16Hôpital Necker Enfants Malades APHP, INSERM U1151, Paris, France.
Background and aim: Burosumab is a monoclonal antibody against anti-FGF23, which has been recently approved for treatment of X-linked hypophosphatemia (XLH). Beyond clinical trials, little is known about its efficacy/safety in clinical practice which is the aim of study.
Patients/Methods: 39 children with XLH were switched from conventional therapy to burosumab (starting dose 0.4 mg/kg), because of following indications: non-responder to conventional therapy (persistence of leg deformities, elevated 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: 25 girls/14 boys (mean age of 9.6±3.8 years; 84.6% of subjects (n=33) presented 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 and CaU/CrU were not modified during the treatment. At M6, 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.
Disclosure: The authors declared no competing interests.
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