Immunogenicity of a Mammalian Cell-Derived Recombinant Human Growth Hormone Preparation during Long-Term Treatment

Zeisel, Hans; Lutz, Andrew J.; Petrykowski, W. v.

doi:10.1159/000182380

Cited by 23 publications

(15 citation statements)

References 22 publications

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“…The most frequent ADRs were increased glycosylated hemoglobin, headache, eosinophilia, hypothyroidism and injection-site reactions. The incidence of patients positive for anti-hGH antibodies under treatment with Omnitrope® liquid (3 of 44; 6.8%) was within the range known from other rhGH-containing products [31,32,33]. …”

Section: Discussionmentioning

confidence: 64%

Seven Years of Safety and Efficacy of the Recombinant Human Growth Hormone Omnitrope® in the Treatment of Growth Hormone Deficient Children: Results of a Phase III Study

et al. 2009

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Aim: This phase III clinical study in growth hormone deficiency (GHD) children with growth retardation was designed to compare efficacy and safety of Omnitrope® with Genotropin® and assess the long-term safety and efficacy of Omnitrope®. The results of 7 years of treatment with Omnitrope® are presented. Patients and Methods: Eighty-nine treatment-naïve, prepubertal children with GHD were randomized (part 1) to Omnitrope® lyophilisate (group A, n = 44) or Genotropin® (group B, n = 45) for 9 months and received a subcutaneous dose of 0.03 mg/kg/day. In part 2, patients receiving Omnitrope® lyophilisate continued the same treatment for a further 6 months, while patients on Genotropin® were switched to Omnitrope® liquid for the subsequent 6 months. In part 3, patients in both groups received Omnitrope®liquid for a period up to 69 months. Results: The development of the 4 auxological parameters (height, height SD score, height velocity and height velocity SD score) and IGF-1 and IGFBP-3 levels were comparable between both groups of patients and confirmed the well-known growth response of GHD children to recombinant human GH treatment. Omnitrope® was well tolerated and safe over 7 years of treatment. Conclusion: The clinical comparability between Omnitrope® and Genotropin® was demonstrated within 9 months of treatment. Long-term safety and efficacy of 7 years of treatment with Omnitrope® was proven.

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Section: Discussionmentioning

confidence: 64%

Seven Years of Safety and Efficacy of the Recombinant Human Growth Hormone Omnitrope® in the Treatment of Growth Hormone Deficient Children: Results of a Phase III Study

et al. 2009

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“…Anti-GH and anti-host cell antibodies were measured centrally every 3 months by H.J. Zeisel at the University Children's Hospital, Freiburg [22], Patients were randomly assigned to receive either rhGH (Saizen®, Ares Serono) 18 IU/m2/week administered by daily subcu taneous injection or the same dose of rhGH plus oxandrolone 0.1 mg/kg/day orally for the 1st year of therapy. During the 2nd treat ment year, the rhGH dose was increased to 24 IU/m2/week in patients receiving rhGH alone.…”

Section: Methodsmentioning

confidence: 99%

Recombinant Human Growth Hormone and Oxandrolone in Treatment of Short Stature in Girls with Turner Syndrome

Stahnke¹,

Stubbe²,

Keller³

1992

Horm Res

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91 girls with Turner syndrome (TS) with a mean chronological age (CA) and bone age (BA) of 10.3 ± 2.3 and 8.9 ± 1.9 years, respectively, were randomly assigned to subcutaneous treatment with recombinant human growth hormone (rhGH) alone (n = 47), 2.6 IU/m² body surface area daily or combination treatment (n = 44) with the same dose of rhGH and oxandrolone 0.1 mg/kg body weight orally, for the first 12 months of this study. During the 1 st year of therapy, there was a striking increase in height velocity (HV) in both groups, from 4.0 ± 0.8 to 6.3 ± 1.3 cm/year [HV standard (standards of untreated Turner patients) deviation score (SDS) for CA from 0.0 ± 0.7 to 2.9 ± 1.3] in the rhGH group and from 4.2 ± 1.2 to 8.5 ± 1.7 cm/year (HV SDS-CA from +0.3 ± 1.0 to+5.6 ± 1.6) in the combination group. The difference between the groups was statistically significant (p < 0.01). During the 2nd year of treatment, the rhGH dose was increased to 3.4 IU/m² daily for the rhGH-alone group, whereas in the combination treatment group the oxandrolone dose was reduced to 0.05 mg/kg daily. HV was maintained at significantly higher levels than those prior to treatment, at 5.3 ± 1.1 cm/year (HV SDS-CA:+2.1 ± 1.3) and 6.2 ± 1.5 cm/year (HV SDS-CA:+3.6 ± 1.4) in the rhGH-alone and the combination group, respectively (p < 0.001). After 2 years of treatment, the mean predictable adult height had increased by +3.6 ± 2.4 cm in the rhGH-alone group and by +5.3 ± 3.6 cm in the combination group. Both treatment regimens were very well tolerated although clitoral enlargement was seen in 15 of the 44 girls of the combination group who had been treated with 0.1 mg oxandrolone daily for the 1 st year. Impaired glucose tolerance was infrequently seen in girls of either group and the higher oxandrolone dose of the 1st year affected serum lipoprotein levels. Our data suggest that rhGH may improve adult height in girls with TS. This beneficial effect may be further increased by the addition of a low dose of oxandrolone (0.05 mg/kg/day).

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“…The analytical method used for the quantification of anti-hGH antibodies was a radioprecipitation assay modified according to Zeisel et al [13]. In a one-step procedure, duplicates of the sample (30 µL of serum) were incubated with 170 µL of assay buffer and 100 µL of commercially available 125-iodine-labeled hGH.…”

Section: Methodsmentioning

confidence: 99%

Biological Significance of Anti-GH Antibodies in Children Treated with rhGH

Binder¹,

Heidenreich²,

Schnabel³

et al. 2019

Horm Res Paediatr

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Background: The occurrence of antidrug antibodies is common in children treated with recombinant human growth hormone (rhGH). However, their clinical significance is unclear. Objective: This study aimed to examine the clinical significance of anti-GH antibodies by analyzing the phenotype of patients who tested positive in relation to the quantity of anti-GH antibodies. Method: In this laboratory-based retrospective study encompassing a time span of 6 years, all positive samples were identified, and senders were contacted. Anti-GH antibodies were measured using a radioprecipitation assay; positive samples underwent a confirmatory assay. Results: Out of a total of 104 samples from 66 patients, positive test results were found in 28 samples from 13 patients. Clinical data were available from all but one. The group with positive test results comprised 6 patients with a normal response to GH provocative tests (group A) and 6 with an insufficient response or with isolated GH deficiency (IGHD) type 1A (group B). Diagnoses in group A were neurosecretory dysfunction, bioinactive GH syndrome and constitutional delay of growth and puberty. Diagnoses in group B were IGHD type 1A, septo-optic dysplasia, and cerebral midline defect with multiple pituitary hormone deficiency. Insufficient growth response to rhGH was absent except in one sibling pair with IGHD type 1A and a patient with cerebral midline defect. These patients had the highest concentrations of anti-GH antibodies. Conclusions: The biological significance of anti-GH antibodies seems to be limited to patients with high concentrations of anti-GH antibodies. For all other patients, we recommend a careful “wait and see” strategy and monitoring antibody titers.

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Immunogenicity of a Mammalian Cell-Derived Recombinant Human Growth Hormone Preparation during Long-Term Treatment

Cited by 23 publications

References 22 publications

Seven Years of Safety and Efficacy of the Recombinant Human Growth Hormone Omnitrope® in the Treatment of Growth Hormone Deficient Children: Results of a Phase III Study

Seven Years of Safety and Efficacy of the Recombinant Human Growth Hormone Omnitrope® in the Treatment of Growth Hormone Deficient Children: Results of a Phase III Study

Recombinant Human Growth Hormone and Oxandrolone in Treatment of Short Stature in Girls with Turner Syndrome

Biological Significance of Anti-GH Antibodies in Children Treated with rhGH

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