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Children with short stature maintain height gained after GH dose reduction
Prepubertal children with short stature who achieved catch-up height with growth hormone therapy were able to maintain normal height velocity after a reduction in GH dose, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
In a previous clinical trial focusing on catch-up growth in prepubertal children with and without GH deficiency, Ralph Decker, MD, MSCI, PhD, of the Gothenburg Pediatric Growth Research Center at the Sahlgrenska Academy at the University of Gothenburg, Sweden, and colleagues randomly assigned participating children to individualized GH-dosing based on estimated GH responsiveness and the distance to mid-parental height standard deviation score (SDS) for each child or to a weight-based GH dose for 2 to 3 years. Children assigned to individualized doses who were predicted to respond poorly, they noted, received higher GH doses vs. those predicted to be highly responsive. The design allowed children with and without GH deficiency to be included in the same study.
“However, it was apparent that this GH dose was likely to be unnecessarily high for some children during the maintenance treatment growth period, and therefore a dose-reduction trial was carried out,” the researchers wrote.
For the present maintenance study, researchers followed the same cohort of 98 children (72 boys), including 33 with GH deficiency, to investigate whether a reduced, individualized GH dose could be associated with maintaining channel parallel growth, defined as the achieved prepubertal height SDS goal close to mid-parental height SDS, after a 50% GH dose reduction once catch-up growth was achieved. Children were randomly assigned to half of their previous GH catch-up dose (n = 27) or to continue with their catch-up dose (n = 38) for 2 years or until onset of puberty. A third arm acted as controls (n = 33) and included participants from the standard, weight-based GH-dose group, who continued on the regimen of 43 µg/kg per day. Primary endpoint was the proportion of children in the three groups with individual changes in height SDS within 0.3 at 1 year from trial start. The cutoff was based on normal variation observed in a healthy reference population.
At 1 year, 85% of the intention-to-treat population in the GH-dose reduction group maintained a change in height SDS within 0.3 vs. 41% of children in the unchanged GH-dose group (P = .0055) and 48% in the control group (P = .0047).
In an analysis of secondary endpoints, researchers found that change in insulin-like growth factor I SDS was –0.75 in the dose-reduction group at 3 months (P = .003) and –0.72 at 1 year, vs. 0.15 in the unchanged-dose group at 1 year (P = .005) and 0.05 in the control group at 1 year (P = .02).
Ten adverse events occurred during the study, but were not related to GH treatment, according to the researchers.
“Results of the present study confirm the hypothesis that channel parallel growth, ie, following its SDS line with normal height velocity, could be maintained during the prepubertal period after [catch-up growth] was complete, using a 50% lower dose than the individualized dose that was used during the catch-up period,” the researchers wrote. “Following completion of the catch-up period when children certainly did ‘move up in height toward their peers’ on a GH dose resulting in an attained height SDS close to [mid-parental height] SDS, a majority of prepubertal children maintained height SDS within 0.3, despite the dose reduction.”
The researchers noted that such a GH dose reduction should be accompanied by close monitoring of well-being and metabolic markers, as there is no method for estimation of individual GH responsiveness during the maintenance treatment period before puberty. – by Regina Schaffer
Disclosures: Pfizer supported this study. Decker reports he has received a lecture fee from Merck Serono and a doctoral grant from Pfizer. Please see the study for all other authors’ relevant financial disclosures.