Of the 40 subjects, only 18 provided consent for randomization. Seven of the 10 girls randomized to the treatment group and 6 of the 8 randomized to the control group completed the study to final height measurement. The average age of the treated girls at the start of therapy was 8.07 years; the average duration of treatment was 6.2 years. All participants reached stage 4 breast development, menarche, and a growth velocity of <2 cm per year in the year preceding final height measurement. Mean final height in the treatment group was 155.3 cm compared to 147.8 cm in the control group—a 7.5-cm difference (95% confidence interval [CI], 3.14-11.86 cm).2,3
A double-blind, placebo-controlled RCT published after the Cochrane review assessed final height in a peripubertal, predominantly male population with non-growth-hormone-deficient short stature.4 Inclusion criteria comprised a height SDS <–2.50, but 6 participants with a height SDS between –2.25 and –2.5 were included because of a change in the criteria.5 Sixty-eight children were initially randomized. Of the 37 randomized to treatment, 22 were available for final height measurement. The placebo group had a higher dropout rate—only 11 of 31 patients were available for final height measurement. In an attempt to reduce the dropout rate, the final height criterion for discontinuation of injections was changed from <0.5 to <1.5 cm per year. The mean age of the treatment group was 12.5 years at initiation of treatment; average duration of treatment was 4.6 years.
Intent-to-treat analysis of patients who received at least 6 months of treatment with final height assessment revealed a positive treatment effect on height (SDS) of 0.51. This is the equivalent of a 3.7-cm difference in final height for the treatment group compared with the placebo group (P<.02; 95% CI, 0.10-0.92 SDS).5
Recommendations
The FDA has approved rGH for use in children with height SDS ≤–2.25—equivalent to the lowest 1.2% of children. The Lawson-Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee states that rGH therapy should be considered only after accurate diagnosis, careful monitoring of growth velocity, and estimation of final height by a pediatric endocrinologist.6,7