ESPE Abstracts (2019) 92 P2-176

Efficacy and Safety of Growth Hormone (GH) in the Treatment of Children with Hypochondroplasia (HCH): Comparison with a Historical Cohort of Untreated Children with HCH

Graziella Pinto1, Dinane Samara-Boustani1, Magali Viaud1, Valérie Cormier-Daire2, Yeriley Lopez3, Laurence Fresneau3, Marie Piketty4, Jean Claude Pineau5, Michel Polak1,6

1Hôpital Universitaire Necker Enfants Malades, Pediatric Endocrinology and Diabetes, Paris, France. 2IMAGINE Institute, Medical Genetics Department, Paris, France. 3Merck s.a.s, Lyon, France. 4Hôpital Necker Enfants Malades, Physiology Laboratory, Paris, France. 5CNRS FRE2029, Paris, France. 6Université Paris Descartes, Paris, France

Hypochondroplasia (HCH) is a skeletal dysplasia, mainly caused by mutations in the fibroblast growth factor receptor3 (FGFR3) gene and characterized by disproportionate short stature.

Our main was to determine the efficacy of growth hormone therapy in children with HCH, compared with a historical cohort of 40 untreated children with HCH.

Diagnosis of subjects was confirmed by the Bone Dysplasia Center2. Height standard deviation scores (SDS) were calculated from historical cohort-growth charts. Nineteen patients with initial height ≤=–2 SDS were treated with Saizen® (r-hGH, Merck France) with an initial dose of 0.05 mg/kg/day (dose adjusted with IGF-I levels). We analyzed only 8 patients (4 males) treated during at least 5 years, at a mean age of 6.8 (± 2.6) yrs.

ResultsBaseline1st yr2nd yr3rd yr5rd yrTotal gain
Height velocity (cm/yr)8.6±1.36.8±1.55.3±1.34.4±1.7
Height (SDS)/Sempe1−2.44±0.7−1.91±0.7*−1.47±0.8*−1.42±0.9*−1.55±0.80.89±0.6*
BMI (SDS)/Sempe11.24±1.21.11±1.01.28±1.21.52±1.01.00±1.1−0.2±1.4
Height / HCP2 (SDS)0.53±0.91.32±0.8*1.91±1.1*2.12±1.3*2.10±1.11.57±0.8*
Upper segment (SDS)−0.44±1.30.12±1.1*0.46±1.3*0.91±1.4*0.99±0.91.43±1.2*
% Total fat mass (SDS)1.33±0.90.30±0.4*0.22± 0.8*0.18±1.0*0.52±1.1*−0.81±0.8*
*P<0.011 vs Sempé; 2 vs values of a non-treated historical cohort HCH

The height gain was +0.89 (± 0.60) SDS compared with French standard population (Sempé), but it was +1.57 (± 0.8) SDS with the historical cohort. Correlation in height gain was observed (P=0.04) between the first and fifth year. Difference in height gain between 5 patients with FGFR3 mutation (1.2 ± 0.8 SDS) and the 3 patients without (2.1 ± 0.6 SDS) was not significant (P=0.12). Seven patients reached near final height SDS: −1.67 ± 0.8 vs Sempé but +2.05 ± 1.1 vs the historical HCH cohort. No treatment related serious adverse-events were reported.

Conclusion: GH is effective in improving growth in some patients with HCH. Response during the first year is predictive of final response (r=0.78, P<0.05) and could be used to decide to continue treatment until final height.