Five-year follow-up of growth hormone antibodies in growth hormone deficient children treated with recombinant human growth hormone.

Objective: The aim was to investigate the long-term evolution of circulating growth hormone antibodies (GH-AB) during and after treatment with methionyl-recombinant human growth hormone (met-rhGH).

Design And Patients: The investigation was performed on serum samples of 46 growth hormone deficient children, treated for at least 12 months with met-rhGH. Twenty patients had never been treated with hGH (previously untreated patients, Group I). Twenty-six subjects were previously treated with pituitary extracted hGH (treated patients, Group II).

Measurements: Serum levels of GH-AB were measured by radioimmunoassay using charcoal precipitation of free ligand.

Results: Fifteen patients (75%) of Group I and three patients (12%) of Group II developed GH-AB. In 15 GH-AB positive patients the antibodies became detectable during the first year of treatment with met-rhGH. In three patients, however, the GH-AB appeared during the second year. Once present, the GH-AB remained detectable throughout the period of treatment with met-rhGH. In six patients in whom treatment with met-rhGH was stopped, GH-AB levels decreased rapidly. In nine patients in whom treatment with met-rhGH was changed to rhGH, the levels of GH-AB decreased and ultimately became undetectable. In two patients GH-AB remained present during administration of rhGH. No effect of GH-AB on the growth-promoting effect of met-rhGH could be documented, either during the first or during the second year of treatment.

Conclusions: This study confirms the high immunogenicity of met-rhGH, especially in patients not treated earlier with hGH. Once present, the GH-AB remain detectable throughout the period of treatment with met-rhGH. After stopping met-rhGH treatment or changing to rhGH the GH-AB disappear rapidly in most patients. No effect of GH-AB on the growth-promoting effect of rhGH could be documented.