Description of the SAGhE Cohort: A Large European Study of Mortality and Cancer Incidence Risks after Childhood Treatment with Recombinant Growth Hormone

Abstract

Background: The long-term safety of growth hormone treatment is uncertain. Raised risks of death and certain cancers have been reported inconsistently, based on limited data or short-term follow-up by pharmaceutical companies. Patients and Methods: The SAGhE (Safety and Appropriateness of Growth Hormone Treatments in Europe) study assembled cohorts of patients treated in childhood with recombinant human growth hormone (r-hGH) in 8 European countries since the first use of this treatment in 1984 and followed them for cause-specific mortality and cancer incidence. Expected rates were obtained from national and local general population data. The cohort consisted of 24,232 patients, most commonly treated for isolated growth failure (53%), Turner syndrome (13%) and growth hormone deficiency linked to neoplasia (12%). This paper describes in detail the study design, methods and data collection and discusses the strengths, biases and weaknesses consequent on this. Conclusion: The SAGhE cohort is the largest and longest follow-up cohort study of growth hormone-treated patients with follow-up and analysis independent of industry. It forms a major resource for investigating cancer and mortality risks in r-hGH patients. The interpretation of SAGhE results, however, will need to take account of the methods of cohort assembly and follow-up in each country.

GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults

“…A full description of the cohort and the methodologies that are being used to assess mortality and cancer incidence risks is provided in Swerdlow et al . (published after the workshop was held) (6) .…”

Long‐term safety of growth hormone—A combined registry analysis

“…Although the validity of the French cohort study has since been questioned, it has nevertheless brought the long‐term safety profile of GH to the forefront. The SAGhE study collected data from cohorts of patients from 8 European countries who were treated with GH in childhood since the first use of this treatment in 1984 and followed them for cause‐specific mortality and cancer incidence …”

“…The SAGhE study collected data from cohorts of patients from 8 European countries who were treated with GH in childhood since the first use of this treatment in 1984 and followed them for cause-specific mortality and cancer incidence. 13 The aim of this literature review was to evaluate long-term safety data from pharmaceutical company GH registries, focusing on mortality, neoplasms, cerebrovascular events and diabetes, to provide clinicians with a useful and comprehensive summary of postmarketing safety data on GH. Here, we present long-term follow-up data collected over a similar time frame to SAGhE.…”

Growth Hormone Deficiency: Diagnosis and Therapy in Children

“…Interestingly, the analysis was independent of industry. The preliminary results are, however, contrasting [92]. In fact, the French SAGhE has raised concerns of increased mortality risk due to bone tumours or cerebral haemorrhage during follow-up into adulthood, especially in patients who had received high GH doses during childhood [93].…”