medwireNews: Most children continue on a normal growth trajectory if their recombinant human growth hormone (GH) dose is reduced by half after they have achieved catch-up growth, shows a randomised trial.

Considering the long duration of GH treatment, “the ultimate goal” after children have achieved catch-up growth should be to use the lowest effective dose that maintains a normal growth velocity, say Ralph Decker (University of Gothenburg, Sweden) and study co-authors.

Their trial, which is published in The Journal of Clinical Endocrinology & Metabolism, included 98 patients who had achieved catch-up growth after 2–3 years of treatment with GH at an individualised dose. They were randomly assigned to continue on the same dose, to have their dose reduced to 50% of that used to achieve catch-up growth or to receive a fixed weight-based dose of 43 μg/kg per day.

The researchers concede that the 50% dose reduction was arbitrary, due to lack of evidence, but say that since it was a proportion of the previous individualised dose it still accounted for individual variation in GH response. They also note that they reduced the GH dose abruptly “[f]or scientific reasons”, which appeared to result in a high rate of “subjective impairments in well-being with fatigue, disturbance in attention and depressed mood” in this group.

During the first year after randomisation, 85% of children in the reduced dose group achieved the primary endpoint of a change in height standard deviation score (SDS) that was no more than +0.3 and no less than –0.3.

The proportions of children achieving this endpoint was significantly lower in the groups that continued on their catch-up growth dose and switched to a fixed weight-based dose, at 41% and 48%, respectively. The same was true in the per-protocol population of 86 children; exclusions included six children who had entered puberty within 9 months of randomisation.

Of note, weight and BMI SDS did not change in the reduced-dose group, but increased significantly in the other two groups.

Baseline insulin-like growth factor (IGF)-1 SDS was higher in the reduced-dose group than the other two, at +2.3 versus +1.7 to +1.8. But this declined significantly over the first 3 months of treatment, to +1.5, compared with no change in the other groups.

Thirty-three of the trial participants had confirmed GH deficiency based on an arginine–insulin stimulation test or their 24-hour GH profile, but 65 had other causes of short stature. The researchers note that this mixture of diagnoses “may be regarded as a critical issue” with their study, although they say that the two groups had similar responses to the GH dose reduction.

Decker and team stress that GH dose reductions “must be accompanied by close monitoring of […] well-being and metabolic markers as presently there is no method for estimation of individual GH-responsiveness during the maintenance treatment period before puberty.”

As such they currently “do not recommend decreasing the dose by 50% in clinical settings”.

By Eleanor McDermid

J Clin Endocrinol Metab 2018; doi:10.1210/jc.2018-01006

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