Implications of a Data-Driven Approach to Treatment with Growth Hormone in Children with Growth Hormone Deficiency and Turner Syndrome

Abstract

BackgroundResponse to growth hormone (GH) therapy may vary between individual patients. Therefore the use of GH in children should be closely monitored to avoid over, under, or ineffective treatment regimens. The treatment response can be evaluated using growth prediction models. In an effort to improve the accuracy of these prediction models, Ranke et al. (J Clin Endocrinol Metab 95(3):1229–37) proposed a novel ‘data-driven’ approach based on a quantitative analysis of a large cohort of patients from the Pfizer International Growth Database (KIGS) treated with Genotropin (human growth hormone). This model allows physicians to predict and evaluate the level of growth response and responsiveness for their patients so they can adapt treatment accordingly. By comparing the actually observed and the predicted growth response the ability of an individual to respond to GH (responsiveness) can be estimated and further treatment can be adapted accordinglyObjectiveTo determine the potential population level reduction in the amount of GH used and impact on height outcome of using this data-driven approach to guide treatment decisions, compared to conventional, ‘experience-based’ GH treatment in prepubertal patients with growth hormone deficiency (GHD) or Turner syndrome (TS).MethodsA model was developed to study the height outcome and the total amount of GH used in the presence or absence of data-driven treatment decisions. The proportion of patients for whom height outcome could be improved or GH use could be reduced (i.e. for low compliance, high or low responder) was estimated using the KIGS cohort. The analysis assumed that this segmentation allows physicians to tailor dosage to the individual patient’s needs or even to discontinue therapy when it is not effective. The analysis used a 4-year time horizon, with Germany as an example country, but results are extendable to other countries. Only the total amount of GH used was included, and effects were defined as the height outcome after 4 years.ResultsThe analysis estimated that an evidence-driven approach may reduce the total amount of GH utilized by 7.0 % over 4 years for the treatment of short stature in prepubertal patients with GHD and TS in Germany. Despite the reduction in drug use the average growth outcomes remained unaffected with the new treatment approach. Univariate and probabilistic sensitivity analyses showed that the results are robust.ConclusionsOur analysis showed that using a data-driven approach to guide treatment decisions for children with GHD or TS is estimated to result in efficiencies in the amount of GH used, without reducing the average growth in the population.

Individualised growth response optimisation (iGRO) tool: an accessible and easy-to-use growth prediction system to enable treatment optimisation for children treated with growth hormone

“…If a child's growth is as predicted and the responsiveness is as expected, GH therapy should be continued at the same dose. Kaspers et al [7] reported that by using population modelling, a small proportion of patients may respond better than predicted and, therefore, their GH dose could be reduced, resulting in a more cost-effective therapy. On the other hand, a proportion of patients may not respond as well as expected.…”

“…However, each child responds to a dose of rhGH in a unique way due to their genetic, metabolic and physical characteristics. Whilst many children with a given diagnosis respond as expected to rhGH treatment and are likely to reach the goals of intended treatment [5], some children respond less well [6] and some may respond better than expected [7].…”

Effects of recombinant human growth hormone therapy on carbohydrate, lipid, and protein metabolisms of children with Turner syndrome

“…1 It is one of the most common genetic disorders, affecting approximately one in every 2,000 live-born females. 2 , 3 Girls with TS typically experience gonadal dysfunction and short stature.…”

Growth Hormone Therapy for Paediatric Growth Disorders: The Past, Present, and Future

“…Despite the major therapeutic advance that use of rhGH represents, there remains considerable variability of long-term growth response, with many patients not achieving their genetic potential, even in classical GH deficiency [37]. To address this variability, a range of models can predict the growth response to GH therapy given for different indications [38][39][40][41][42]. Working from such models, height velocity using a standard dose of rhGH 0.3 mg/kg/week will increase by 2 cm/year in children with GH deficiency, compared with SGA and Turner syndrome patients.…”