Latest GeNeSIS data confirm rhGH efficacy and long-term safety profile
medwireNews: Two reports from the GeNeSIS observational study reveal the latest growth data and confirm that the safety profile of recombinant human growth hormone (rhGH) “remains favourable”.
However, Christopher Child (Eli Lilly and Company, Windlesham, UK) and study co-authors note in The Journal of Clinical Endocrinology & Metabolism that the average follow-up time for the safety study, of 4.2 years, was “relatively short”.
A total of 22,311 rhGH-treated patients were enrolled into GeNeSIS, including 63% with GH deficiency (79% idiopathic and 21% organic), 13% with idiopathic short stature, 8% with Turner syndrome and 6% who were born small for gestational age. Other diagnoses included SHOX deficiency, chronic renal insufficiency, clinical syndromes and skeletal dysplasias.
The highest rates of adverse and serious adverse events occurred in patients with organic GH deficiency and chronic renal insufficiency, which the researchers note is consistent with “the severity of the underlying medical conditions”.
The only significantly elevated adverse effect was type 2 diabetes, with the 18 cases detected among 21,448 patients equating to a significantly increased standardised incidence ratio of 3.77. This increase occurred mostly among girls with Turner syndrome (three cases) and patients with organic GH deficiency (eight cases), and 72% of the patients had diabetes risk factors.
Child and team therefore advise “that clinicians should focus efforts at lifestyle interventions in GH-treated patients with [type 2 diabetes] risk factors.”
The mortality rate was no higher than expected and neither were the rates of cerebrovascular disease or primary cancers. The most common cancer was lymphoma, and this had a nonsignificantly increased standardised incidence ratio of 1.93; four of the five cases occurred in Germany, for which the researchers have no explanation.
There were 85 recurrent neoplasms among 74 of the 1087 children who had a history of cancer, as well as 34 second cancers among 31 of 622 childhood cancer survivors, although Child and team found no evidence for an increased risk in rhGH-treated patients.
They conclude: “Although the GeNeSIS data are reassuring overall, specific safety findings emphasise the need to monitor GH-treated patients for abnormalities in glucose metabolism and those with a history of previous neoplasm and irradiation for development of subsequent neoplasms.”
The latest growth outcomes are reported in Hormone Research in Paediatrics for 9157 children treated in France, Germany and the USA who were treatment-naïve at study entry.
The average starting dose of rhGH varied from 0.20 mg/kg per week in Germany to 0.33 mg/kg per week in the USA. Nonetheless, children in all three countries made significant gains in their height standard deviation score (SDS), report Heike Jung (Lilly Deutschland, Bad Homburg) and co-researchers.
Children with GH deficiency achieved average SDS gains greater than 1.0 and a near-adult height SDS greater than –1.0, whereas those with other diagnoses made smaller gains, although near-adult height SDS was greater than –2.0, on average, from a starting point of around –2.5.
Irrespective of diagnosis, most catch-up growth occurred during the first year of rhGH treatment.
“It has been suggested that discontinuation of GH treatment before reaching adult height or [near-adult height] may result in catch-down growth and a loss of height SDS gain from GH treatment for some patients”, the researchers comment.