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Recombinant human growth hormone for children born small for gestational age: Meta-analysis confirms the consistent dose-effect relationship on catch-up growth

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Abstract

Background: The optimal treatment regimen of recombinant human GH (r-hGH) for short children born small for gestational age (SGA) is still under discussion. Methods: A metaanalysis was performed of existing clinical trials that investigated the treatment of r-hGH in short children diagnosed SGA or with intrauterine growth retardation to determine the relationship between the daily r-hGH dose (placebo/no treatment; 0.033 mg/kg/day; 0.067 mg/kg/day) and the effect on growth [change in height-SD score (SDS) for chronological age]. A mathematical model describing the dose-response relationship was produced, and growth response (gain in height-SDS) to 2 yr of r-hGH 0.033 mg/kg/day [somatropin (rDNA origin) for injection; Serono] was estimated and compared with the response to other r-hGH formulations. Results: The relationship between r-hGH dose and 2-yr growth response was described by an equation. The equation yielded a mean difference in height-SDS gain of 0.48 (0.35) between r-hGH 0.033 and 0.067 mg/kg/day in favor of the higher dose. The height-SDS gain after 2 yr of Serono r-hGH formulation, 0.033 mg/kg/day was estimated as 1.2. Comparison of this estimate to the growth response to 2-yr treatment at 0.033 mg/kg/day of other r-hGH formulations (mean difference in height-SDS 0.05, lower limit of the 95% confidence interval=−0.15) confirmed that growth response to Serono r-hGH formulation 0.033 mg/kg/day is an inferred response estimated to be within the range of observed responses to a (non-Serono formulation) r-hGH dose of 0.033 mg/kg/day. Conclusion: There is a clear dose-response relationship for r-hGH in the treatment of short children born SGA and the analysis confirmed that treatment with Serono r-hGH formulation 0.033 mg/kg/day should provide a meaningful therapeutic response.

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Authors and Affiliations

  1. Debiopharm SA, Lausanne, Switzerland

    R. Crabbé

  2. Merck Serono International SA, chemin des Mines 9, CH-1211, Geneva 20, Switzerland

    M. von Holtey & P. Engrand

  3. Hôpital Debrousse, Service d’endocrinologie-pédiatrie, Lyon, France

    P. Chatelain

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  1. R. Crabbé
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  2. M. von Holtey
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  3. P. Engrand
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  4. P. Chatelain
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Correspondence to M. von Holtey.

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Crabbé, R., von Holtey, M., Engrand, P. et al. Recombinant human growth hormone for children born small for gestational age: Meta-analysis confirms the consistent dose-effect relationship on catch-up growth. J Endocrinol Invest 31, 346–351 (2008). https://doi.org/10.1007/BF03346369

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