BUROSUMAB IN ADULT PATIENTS WITH X-LINKED HYPHOPHOSPHATEMIC RICKETS: AN ITALIAN EXPERIENCE

Abstract BACKGROUND AND AIMS X-linked hypophosphoremic rickets (XLH) is a rare disease caused by mutations in the PHEX gene leading to an increase in the serum levels of FGF23, which inhibits the tubular reabsorption of phosphates and the production of 1,25(OH)2D. These alterations cause hypophosphatemia, rickets, bone deformities, growth retardation and muscle activity impairment. METHOD Burosumab (B) is a monoclonal antibody against FGF23, used for the treatment of XLH. In Italy B can be employed in adults only as compassionate use. In 2020, we treated four adult XLH patients with B (1 mg/kg sc every 4 weeks) for 24 weeks. These patients, V.M. (M, 32 years), S.T. (F, 47), E.R. (M, 46) and S.M. (F, 20) had legs deformities, musculoskeletal pain and severe disability. RESULTS In all patients, phosphorus levels were normalized by B 2 weeks after the B injection, but its levels decreased during the following 28 days; the effect of B on serum phosphate declined during the 24-week follow-up. Plasma values of 1,25(OH)2D and CTX (C-terminal telopeptide of type I collagen) increased after burosumab, but their increase was less marked after the first two injections. In contrast, PTH and bALP values did not change during B therapy. Scores of BPI test, chair test and walking test confirmed an improvement in the fatigue resistance and physical performance. Other tests showed the improvement of self-reported well-being and quality of life in all patients. These effects were not observed in adult patients on conventional therapy with phosphate salts and active vitamin D. CONCLUSION Therefore, markers of physical conditions and life quality may be more indicative for the necessity of burosumab treatment than serum phosphate, which may not be a significant marker to initiate burosumab treatment in adult patients. Burosumab treatment of XLH patients is well-tolerated and leads to prolonged beneficial effects on general conditions of patients although the inconstant improvement of serum phosphate.