Growth hormone treatment of Canadian children: results from the GeNeSIS phase IV prospective observational study

Abstract

Background: Country-specific data on outcomes of treatment with recombinant human growth hormone are lacking. We present such data for children treated with growth hormone in Canada.

Methods: We describe characteristics and outcomes of 850 children (mean age at baseline 8.5 yr) treated with growth hormone constituting the Canadian cohort of the multinational phase IV prospective observational Genetics and Neuroendocrinology of Short-stature International Study (GeNeSIS). The diagnosis associated with short stature was as determined by the investigator. Auxological data were evaluated yearly until near-adult height. Adverse events were assessed in all growth-hormone-treated patients.

Results: The diagnosis ascribed as the cause of short stature was growth hormone deficiency in 526 children (61.9%), predominantly organic rather than idiopathic, particularly congenital pituitary abnormalities and intracranial tumours. All diagnostic groups with sufficient patients for analysis had increased height velocity standard deviation score (SDS) and height SDS during growth hormone treatment. For patients who reached near-adult height (n = 293), the mean height SDS was within the normal range for about 80% of patients with organic growth hormone deficiency (n = 131) or idiopathic growth hormone deficiency (n = 50), 50% of patients with idiopathic short stature (n = 10) and 46% of patients with Turner syndrome (n = 79). Eleven deaths were reported, 7 in patients with organic growth hormone deficiency. Serious adverse events considered related to growth hormone treatment (n = 19) were isolated except for medulloblastoma recurrence (n = 2) and adenoidal hypertrophy (n = 2).

Interpretation: Growth hormone treatment was effective and had a good safety profile in Canadian children. Growth hormone dosages were lower than in the US and global GeNeSIS cohorts, and a greater proportion of treated Canadian children had organic growth hormone deficiency.

Study registration: ClinicalTrials.gov, no. NCT01088412.

Conflict of interest statement

Competing interests: Cheri Deal has been involved with phase III and/or phase IV studies with Eli Lilly and Company, Serono, Versartis and OPKO Health, invited lectureships sponsored by Novo Nordisk, Eli Lilly and Company, Pfizer, EMD Serono and Merck Serono, ad hoc consulting with EMD Serono, Novo Nordisk, Merck Serono, Versartis, OPKO Health and Zafgen, and the Grant for Growth Innovation Scientific Advisory Board: Merck. She was a member of the Genetics and Neuroendocrinology of Short Stature International Study International Advisory Board. She has received honoraria and meeting expenses from Eli Lilly and Company. Susan Kirsch and Nan Jia are employees of Eli Lilly and Company. Jean-Pierre Chanoine has received honoraria (speaker fees and advisory board membership) from Eli Lilly and Company. Elizabeth Cummings has received grant support from Eli Lilly and Company and Sanofi. Elizabeth Rosolowsky has received grant support from Eli Lilly and Company and has served on the advisory boards for Insulet and Medtronic. Christopher Child is an employee and stockholder of Eli Lilly and Company. No other competing interests were declared.

Copyright 2018, Joule Inc. or its licensors.

Figures

Figure 1:

Mean height velocity standard deviation score (HV SDS) and height SDS over the first 4 years of growth hormone treatment for patients in Canada and the global population with data for each year who were naive to growth hormone treatment at study entry, for all patients ([A]) and for evaluable diagnostic groups ([B], [C] and [D]). Standard deviation score corresponds to the following height percentiles on a standard height-for-age growth curve: –3 SDS = 0.2%, –2 SDS = 2.3%, –1 SDS = 16.0%, 0 SDS = 50.0%, 1 SDS = 86.0%, 2 SDS = 97.7%, 3 SDS = 99.8%. Data for patients with idiopathic short stature are not shown because of the small number of patients (n = 9) in this diagnostic group in Canada with relevant data. Grey shading delineates “normal” values within ± 2 SDs. Error bars = 95% confidence intervals.

Figure 2:

Change in height standard deviation score (SDS) from baseline to near-adult height for all growth-hormone–treated patients and by diagnostic group in Canada and the global population. Data for patients with idiopathic short stature are not shown because of the small number of patients (n = 10) in this diagnostic group in Canada with relevant data. Error bars = 95% confidence intervals. Note: GHD = growth hormone deficiency.