medwireNews: Children with short stature benefit from receiving combined treatment with growth hormone (GH) and insulin-like growth factor (IGF)-1, if they have low endogenous levels of the latter, a study shows.

Children receiving recombinant human (rh)GH in the open-label randomised trial achieved better growth velocity during the first year of treatment if they were also given rhIGF-1. The rhIGF-1 doses trialled were 50, 100 and 150 µg/kg, in addition to 45 µg/kg recombinant hGH as once daily therapy, with the highest rhIGF-1 dose resulting in a significant improvement.

Martin Savage, Emeritus Professor of Paediatric Endocrinology from Barts and the London School of Medicine & Dentistry, UK, who was not involved in the study, called it “a courageous attempt to test the hypothesis that, as in human physiology, GH and IGF-1 have independent and complementary effects in childhood linear growth”, and described the results as “striking”.

During the first year of treatment, the average height velocity among the 25 children given hGH alone was 9.3 cm/year. Children given rhIGF-1 had greater height velocity, on average, at 10.1, 9.7 and 11.2 cm/year for children given the 50, 100 and 150 µg/kg doses, respectively (27, 27 and 26 patients, respectively).

During the second and third years of treatment, there were no significant differences in height velocity between children given monotherapy and combination therapy. However, the first-year gains in height velocity translated to a greater improvement in height by the end of the study, Philippe Backeljauw (Cincinnati Children’s Hospital Medical Center, Ohio, USA) and co-researchers report in Hormone Research in Paediatrics.

At baseline the children’s average height standard deviation score (SDS) was about –2.5. But by the end of the third year of treatment, the patients given hGH monotherapy had an average height SDS gain of 1.3, whereas those also given 50, 100 and 150 µg/kg IGF-1 had larger gains of 1.6, 1.8 and 1.9, respectively, with the two highest doses resulting in significantly larger gains than hGH alone.

The increased growth was not accompanied by excess bone maturation, however, with bone age change being similar in all four treatment groups.

The team found the safety profile of combined hGH and rhIGF-1 treatment to be similar to that of the individual therapies. Most adverse events were mild and quickly resolved. Ten patients withdrew from the study because of adverse events, with six of these thought to be related to treatment (injection site pain, alopecia, neck pain, urticaria and drug hypersensitivity). There were two cases of intracranial hypertension, which lead to rhIGF-1 dose reduction, but not discontinuation.

“Paediatric endocrinology is historically littered with abandoned protein preparations after failed attempts to surpass the efficacy of hGH in growth disorders”, Savage told medwireNews.

“Although hormone therapy in idiopathic short stature remains controversial and is not universally adopted, an obvious indication for further studies of this combined treatment is in poor responders with GH deficiency,” he said.

“This is an unmet clinical need. My heartfelt plea, in the light of these positive results, would be to give hGH plus rhIGF-1 therapy a chance.”

By Eleanor McDermid, Senior medwireNews Reporter

Horm Res Paediatr 2015; Advance online publication

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