Endocrine Abstracts

Introduction: in X-linked hypophosfatemic rickets (XLH) mutations of PHEX lead to elevated FGF-23 levels. Phosphate salts and calcitriol represented the only treatment option. Tertiary hyperparathyroidism (THPT) is a complication of XLH worsening the clinical features and constituting a contraindication to conventional treatment. Burosumab, a monoclonal antibody anti-FGF23, was recently approved in XLH. No data about Burosumab treatment in patients with XLH and THPT are available.

Patients: two patients (M 61, F 67 yrs) affected with XLH and THPT were treated with Burosumab (standard dose 1 mg/kg/28 days). Its compassionate use was approved by local Ethics Committees (Fondazione Ca’Granda Milan and Papa Giovanni XXIII Bergamo, Italy, for patients M and F, respectively).

Results: values at baseline in M and F, were, respectively, phosphoremia 1.4 and 1.4 mg/dl, Ca++ 1.53 and 1.39 mmol/l (1.13-1.32), PTH 76.4 and 91.75 ng/l (6.5-36.8), 25OHvitamin D 31.8 and 46.4 μg/l, creatinine 1.14 and 0.87 mg/dl, TmP/GFR 0.33 and 0.35 mg/dl, ALP 78 and 110U/l, CTX 846 and 902 ng/l. At 1 month: phosphoremia 2.27 and 2.2 mg/dl, Ca++ 1.57 and 1.45 mmol/l, PTH 95.2 and 70 ng/l, TmP/GFR 0.63 and 0.59 mg/dl, ALP 78 and 130 U/l, CTX 2250 and 1405 ng/l. At 6 months: phosphoremia 1.74 and 2.1 mg/dl, Ca++ 1.55 and 1.39 mmol/l, PTH 75 and 65 ng/l, TmP/GFR 0.41 and 0.52 mg/dl, ALP 78 and 130 U/l, CTX 1910 and 1605 ng/l. In both patients an improvement in myalgias, arthralgias and mood was noticed. At 6 months six-minute walk test in M improved (455 m vs 335 m at baseline, +36%). In M, after the introduction of cinacalcet at 3 months, calcium and PTH levels decreased without normalization and minimal effects on phosphoremia and TmP/GFR were observed. At 6 months in M we increased Burosumab dose to 1.2 mg/kg/28 days and the patient showed further improvement of symptoms at 9 months (pain assessed through VAS score decreased from 3 at 6 months and 5 at baseline to 2), despite persistent hypophosphatemia (phosphoremia 2.28 mg/dl, TmP/GFR 0.5 mg/dl).

Conclusions: Burosumab, in XLH complicated with THPT, ameliorates the symptoms, without normalizing phosphoremia, and in this subset of patients a higher dose may be needed. Clinical improvement despite hypophosphatemia could suggest a direct role of FGF-23 in the development of symptoms.