A 4-Year, Open-Label, Multicenter, Randomized Trial of Genotropin® Growth Hormone in Patients with Idiopathic Short Stature: Analysis of 4-Year Data Comparing Efficacy, Efficiency, and Safety between an Individualized, Target-Driven Regimen and Standard Dosing

Abstract

Background/Aims: Growth hormone (GH) treatment regimens for children with non-GH-deficient, idiopathic short stature (ISS) have not been optimized. To compare the efficacy, efficiency, and safety of an individualized, target-driven GH regimen with standard weight-based dosing after 4 years of treatment. Methods: This is a 4-year, open-label, multicenter, randomized trial comparing individualized, formula-based dosing of Genotropin® versus a widely used ISS dose of Genotropin®. Subjects were prepubertal, had a bone age of 3-10 years for males and 3-9 years for females, were naive to GH treatment, and had a height standard deviation score (Ht SDS) of -3 to -2.25, a height velocity <25th percentile for their bone age, and peak stimulated GH >10 ng/ml. After the first 2 years, the individualized-dosing group was further randomized to either 0.18 or 0.24 mg/kg/week. Results: At 4 years, subjects in all treatment regimens achieved similar average height gains of +1.3 SDS; however, the individualized dosing regimen utilized less GH to achieve an equivalent height gain. Conclusion: Individualized, formula-based GH dosing, followed by a dose reduction after 2 years, provides a more cost-effective growth improvement in patients with ISS than currently employed weight-based regimens.

Growth hormone in combination with leuprorelin in pubertal children with idiopathic short stature

“…The adverse events reported in the study were consistent with the safety profile of GH in patients with ISS, and IGF-I was not increased excessively ( 1 , 3 , 8 , 31 , 32 ). Because GnRH agonist therapy is associated with decreased BMD, concerns have been raised concerning potential fractures due to the reduced bone accretion ( 12 ).…”

“…Various studies have shown that growth hormone (GH) treatment of children with ISS can increase their growth velocity and, to a lesser extent, adult height ( 1 , 2 , 3 , 4 , 5 , 6 ). The effect on height is variable and depends, among other factors, on dose and age at GH initiation ( 7 , 8 , 9 , 10 ). GH treatment for ISS was approved in the United States in 2003 and has not been approved in the EU ( 4 ).…”

Advances in paediatrics in 2016: current practices and challenges in allergy, autoimmune diseases, cardiology, endocrinology, gastroenterology, infectious diseases, neonatology, nephrology, neurology, nutrition, pulmonology

“…Consistently, the use of Genotropin®, a biosimilar product, has been studied in an open-label, multicenter, randomized trial. After 4 years of treatment, 316 children with idiopathic short stature in all treatment regimens achieved similar average height gains; however, the individualized dosing regimen utilizing less GH reached an equivalent height gain [ 37 ].…”

Cost-Conscious Growth-Promoting Treatment: When Discretion Is the Better Part of Value

“…Growth responses vary without a clear relationship between hGH dose and height SDS change in children with ISS [32] who often have presentations and laboratory findings similar to partial IGHD. In such children, results vary as to whether individualized GH responsiveness formula-based hGH dosing does [33] or does not [34] achieve targeted height gain during the first years of treatment with lower variability. Thus, in practice, it is still reasonable to initiate hGH treatment at a dose typically used to treat GHD and then titrate upward as needed to sustain a desired growth rate [35].…”

“…Thus, in practice, it is still reasonable to initiate hGH treatment at a dose typically used to treat GHD and then titrate upward as needed to sustain a desired growth rate [35]. Importantly, following a period of catch-up growth, hGH doses – and costs – can usually be reduced without decline in height SDS [34]. While short-term data suggest that targeting hGH dosing to IGF-1 levels may improve growth response [36], it is not known whether adult height is improved, or long-term risks increased [37] by such titration, and more to the point, whether such hGH dose escalation is a necessary or cost-conscious approach to achieving a satisfactory therapeutic objective.…”