medwireNews: Treating children with idiopathic short stature (ISS) with an individualised, formula-based dose of recombinant human growth hormone (rhGH) induces equivalent catch-up growth to that achieved with a standard dose, show findings from a randomised trial.

Moreover, the results show that using individualised formula-based treatment during the first 2 years, followed by a reduced maintenance dose, could allow children to achieve their predicted adult height with rhGH doses that are overall around a third lower than the standard weight-based dose of 0.37 mg/kg per week.

The resulting lower cost “becomes particularly important in situations when insurer policies limit the GH dosage that can be prescribed or when the family is required to pay for the overall treatment costs due to a lack of insurance coverage”, say Debra Counts (University of Maryland School of Medicine, Baltimore, USA) and co-researchers in Hormone Research in Paediatrics.

The formula-based dosing, based on a Swedish growth prediction model, involved predicting patients’ change in height standard deviation score (SDS) from 10 variables including their pre-baseline weight, height and growth variables, and parental height SDSs. The team then compared the predicted change in height SDS to dose-response curves from the literature to determine the optimal rhGH dose needed to obtain target height SDS.

During the first 2 years of treatment, representing the catch-up phase, both the 202 children assigned to formula-based rhGH dosing and the 114 assigned to receive the standard dose achieved an average 1.0 increase in height SDS.

Over this period, the formula-based dosing group received a median dose of 0.41 mg/kg per week, but the actual dose used ranged from 0.10 to 0.72 mg/kg per week.

At the end of the catch-up phase, the standard-dose group continued on the same dose for a further 2 years of maintenance therapy, but patients in the formula-based group were randomly assigned to receive a lower weekly dose of 0.18 or 0.24 mg/kg.

By the end of the maintenance phase, the height gain over the whole 4 years was 1.3 SDS for the standard group, and also for the 0.18 and 0.24 mg/kg groups. But during the maintenance phase, patients taking the 0.18 and 0.24 mg/kg doses used an average 61.1 and 73.3 mg rhGH per cm gained, compared with 93.7 mg/cm in the standard-dose group.

Because all three groups achieved the same height gain, this indicates that growth during the maintenance phase is not dose-dependent and, “therefore, represents an important finding that differs from the traditionally held belief that patients with ISS generally require higher-than-average GH dosing due to intrinsic GH resistance”, say Counts et al.

They note that the dose reduction between the catch-up and maintenance phases for children in the formula-based group averaged 51% and, in some cases, was as much as 60%.

This knowledge “should lead to lower overall dosing and meaningful improvements in GH drug utilization”, they add.

By Eleanor McDermid, Senior medwireNews Reporter

Horm Res Paediatr 2015; Advance online publication

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