Growth Response to Recombinant Human Growth Hormone of Mammalian Cell Origin in Prepubertal Growth Hormone-Deficient Children during the First Two Years of Treatment

Abstract

In five clinical studies performed in Austria, France, the FRG, Italy, Switzerland, the UK and the USA, 304 growth hormone (GH)-deficient children were treated with recombinant human GH (rhGH) of mammalian cell origin. Two hundred and twenty-five patients were previously untreated (naive patients), and 79 were transferred from pituitary hGH after interruption of therapy for at least 6 months (transfer patients). Two treatment protocols, differing in both dose and frequency of injections, were used: (1) a dose of 0.6 IU/kg body weight per week was administered in 3 s.c. injections to 203 patients (178 naive, 25 transfer; group 1); and (2) a dose of 0.45 IU/kg body weight per week was administered in 7 s.c. injections to 101 patients (47 naive, 54 transfer; group 2). After 1 and 2 years of treatment, 143 and 109 naive, and 51 and 46 transfer patients, respectively, were still prepubertal, and their data were analyzed for efficacy. During the 1 st year of treatment, both naive and transfer patients on daily injections (group 2) demonstrated better growth than those on 3 injections per week (group 1), with height velocities (HVs) of 10.6 ± 2.7 cm/year (group 2) versus 8.6 ± 2.0 cm/year (group 1) for naive patients (p < 0.001), and 9.9 ± 1.9 cm/year (group 2) versus 7.2 ± 2.7 cm/year (group 1) for transfer patients (p < 0.001). The corresponding changes in height standard deviation score (ΔH SDS) for chronological age (CA) were + 1.3 ± 0.6 (group 2)versus + 0.8 ± 0.5 (group 1) for naive patients (p < 0.01), and+ 1.1 ± 0.3 (group 2) versus + 0.6 ± 0.4 (group 1) for transfer patients (p < 0.001). For the 2nd treatment year, statistically significant between-group differences in HV and ΔH SDS-CA were seen only in transfer patients, with HVs of 6.8 ± 1.2 (group 2) versus 5.0 ± 1.6 cm/year (group 1) (p < 0.001) corresponding with ΔH SDS of+0.6 ± 0.3 versus +0.2 ± 0.3 (p < 0.001). In naive patients, the mean HV and the corresponding ΔH SDS-CA during the 2nd year were similar in both groups, with an HV of 7.1 ± 1.2 cm/year (group 2) versus 6.6 ± 1.4 cm/year (group 1), and ΔH SDS-CA of+ 0.44 ± 0.29 versus +0.41 ± 0.30, respectively. RhGH treatment was very well tolerated and only 7 patients (2 %) developed anti-hGH antibodies of low affinity and binding capacity persisting longer than 3 months. Thus, authentic rhGH produced in mammalian cells is both efficacious and safe in the treatment of GH-deficient children.