ESPN 54th Annual Meeting

ESPN 2022


 
Effects of burosumab treatment on mineral homeostasis in children and adolescents with X-linked hypophosphatemia: lessons from the German XLH Registry
EWERT ANNIKA REHBERG MIRKO 2 SCHLINGMANN KARL PETER 3 KEMPER MARKUS 4 DERICHS UTE 5 PATZER LUDWIG 6 STAUDE HAGEN 8 JOHN ULRIKE 7 METZING OLIVER 7 WEITZ MARCUS 9 FREIBERG CLEMENS 10 WÜHL ELKE 11 SCHAEFER FRANZ 11 HIORT OLAF 12 SCHNABEL DIRK 13 HAFFNER DIETER 1

1- DEPARTMENT OF PEDIATRIC NEPHROLOGY, HANNOVER MEDICAL SCHOOL, HANNOVER, GERMANY
2- 2DEPARTMENT OF PEDIATRICS, UNIVERSITY OF COLOGNE, COLOGNE, COLOGNE, GERMANY
3- DEPARTMENT OF GENERAL PEDIATRICS, PEDIATRIC NEPHROLOGY, UNIVERSITY CHILDREN’S HOSPITAL, MÜNSTER, GERMANY
4- ASKLEPIOS CHILDREN’S HOSPITAL HAMBURG-HEIDBERG, HAMBURG, GERMANY
5- UNIVERSITY CHILDREN’S HOSPITAL, MAINZ, GERMANY
6- ST. ELISABETH AND ST. BARBARA CHILDREN’S HOSPITAL, HALLE/SAALE, GERMANY
7- UNIVERSITY CHILDREN’S HOSPITAL, JENA, GERMANY
8- UNIVERSITY CHILDREN’S HOSPITAL, ROSTOCK, GERMANY
9- PEDIATRIC NEPHROLOGY, UNIVERSITY CHILDREN’S HOSPITAL, TÜBINGEN, GERMANY
10- DEPARTMENT OF PEDIATRICS, UNIVERSITäTSMEDIZIN GÖTTINGEN, GÖTTINGEN, GERMANY
11- DIVISION OF PEDIATRIC NEPHROLOGY, CENTER FOR PEDIATRICS AND ADOLESCENT MEDICINE, HEIDELBERG UNIVERSITY HOSPITAL, GERMANY
12- UNIVERSITY CHILDREN’S HOSPITAL LÜBECK, LÜBECK
13- CENTER FOR CHRONICALLY SICK CHILDREN, PEDIATRIC ENDOCRINOLOGY, UNIVERSITY MEDICINE, CHARITè BERLIN, GERMANY
 
Introduction:

Burosumab was approved for treatment of pediatric patients with X-linked hypophosphatemia (XLH). However, data on its efficacy in adolescents (age > 12 years) and in real-world settings are lacking.

Material and methods:

Here we assess the effects of 12 months burosumab treatment on mineral homeostasis in 77 pediatric XLH patients (50 children, 27 adolescents) enrolled in the German XLH Registry. Age and sex related SD scores (SDS) were calculated for serum phosphate and alkaline phosphatase (ALP) levels, and renal tubular reabsorption of phosphate per glomerular filtration rate (TmP/GFR).

Results:

At baseline, all patients presented with profound hypophosphatemia (-4.5 SDS), reduced TmP/GFR (-6.5 SDS), and elevated ALP (2.7 SDS, each p<0.001 versus healthy children) suggesting persisting rickets despite long-term therapy with oral phosphate and active vitamin D. Burosumab treatment resulted in rapid increases in mean serum phosphate and TmP/GFR by approx. 0.3 mmol/l amounting to -2.2 SDS and -2.5 SDS at 12 months, respectively (each p<0.001 versus baseline). This was paralleled by a continuous decrease in serum ALP (1.3 SDS, p<0.001 versus baseline). Serum phosphate, TmP/GFR, and ALP values were normalized in approximately 40%, 30% and 80% of patients, respectively. Two patients had transient hyperphosphatemia due to a dosing error. At 12 months, the median burosumab dosage amounted to 0.8 mg/kg (range 0.6-1.2). Serum phosphate levels at 12 months were comparable between children (-2.3 SDS) and adolescents (-2.1 SDS) and associated with parathyroid hormone (PTH) levels. Serum ALP z-scores were associated with PTH levels in adolescents but not in children.

Conclusions:

In this real world setting 12 months burosumab treatment was effective to normalize serum ALP levels in children and adolescents with XLH suggesting healing of rickets despite persisting mild hypophosphatemia in about half of patients. Elevated PTH levels are a risk factor for failure to normalize mineral homeostasis.