An analysis of the clinical and cost effectiveness of GH replacement therapy before and during puberty: should we increase the dose?
Sasha Howard1,2 & Gary Butler1,2
Background: We aim to investigate the influence of GH on pubertal growth in children receiving GH replacement therapy for GH deficiency.
Methods: We analyse a large dataset of children (n=236) with GH deficiency from the international KIGS database. We examine the relationship between pubertal growth and treatment with GH replacement therapy using linear regression and repeated measures analysis, and the incremental cost benefit of increasing doses of GH during puberty.
Results: Multilevel modelling shows that important predictors for height gain after puberty include gender, age at puberty onset and number of injections of GH/week. Cross-sectional analysis of annual change in height SDS in the 4 years pre- and post-pubertal onset suggests that GH dose has a more significant positive influence on height in the pre-pubertal period, with the effect of GH dose post-pubertal onset more marked in girls and children with multiple pituitary hormone deficiencies. Multilevel modelling revealed a highly significant role for GH dose in the pre-pubertal period (P<0.001) in comparison to a non-significant effect on height gain after pubertal onset (P=0.32). Cost analysis showed that for an average female, use of high dose GH (39 μg/kg per day) at an extra £4,753 per year above the cost of low dose GH (23 μg/kg per day) would result in a gain of ~0.72 cm/year in the pre-pubertal period, compared to a gain of only 0.14 cm/year post-puberty onset.
Conclusion: The influence of GH dose on height gain after puberty onset is at best a modest one. Increasing GH dose to the upper end of the recommended dosage regimen in this period is more likely to have a beneficial effect in girls. Cost analysis reveals that use of high doses of GH after puberty onset has significant cost implications without providing a worthwhile gain in final height for children with GH deficiency.