Burosumab treatment in an adult with FGF23-mediated hypophosphatemia due to cutaneous skeletal hypophosphatemia syndrome.

Context: Cutaneous skeletal hypophosphatemia syndrome (CSHS) is an ultrarare disorder defined by epidermal and/or melanocytic nevi, mosaic skeletal dysplasia, and FGF23-mediated hypophosphatemia. As in other FGF23-mediated hypophosphatemia conditions, individuals with CSHS have renal phosphate wasting and inappropriately normal or frankly low 1,25-dihydroxyvitamin D levels with resultant hypophosphatemia leading to rickets and osteomalacia. Conventional therapy for FGF23-mediated hypophosphatemia consists of multiple daily doses of oral phosphate and active vitamin D. Objective: Burosumab is a fully human immunoglobulin G1 monoclonal antibody that binds to and inhibits the activity of FGF23, leading to an increase in serum phosphorus levels and skeletal healing. Given its efficacy in tumor-induced osteomalacia and X-linked hypophosphatemic rickets, two related disorders of FGF23-mediated hypophosphatemia, we explored treatment with burosumab in a young adult with CSHS. Methods: In this open-label, single-patient trial conducted in the clinical research unit of an academic children's hospital, burosumab was administered subcutaneously every 4 weeks for 3 years. The participant was an 18-year-old woman with CSHS and FGF23-mediated hypophosphatemia. Burosumab was administered subcutaneously every 4 weeks, starting at 0.3 mg/kg/dose and increasing up to 0.9 mg/kg/dose. Main outcome measures included change in blood phosphorus levels. Results: Burosumab therapy was well tolerated with correction of hypophosphatemia and improvement in other measures including renal phosphate loss, alkaline phosphatase, active vitamin D metabolism, skeletal imaging, pain, physical function, and overall quality of life. Adverse events were manageable, with unclear relationship to burosumab treatment. Conclusion: These findings suggest that burosumab may be an effective treatment for CSHS.