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• W4247387715 abstract "<h3>Introduction</h3> Faltering growth is a complication of paediatric Crohn9s disease, affecting up to a third of patients. There is no recognised treatment targeted at improving linear growth. These children have low circulating insulin-like growth factor-1 (IGF-1), a hormone essential for linear growth and the primary mediator of growth hormone (GH) action. Low IGF-1 concentrations occur despite normal GH response to stimulation testing – the children thus having a functional GH insensitivity. Injections with recombinant human IGF-1 (rhIGF-1) have been reported to improve growth in animal models of colitis and in children with genetic GH insensitivity syndrome using doses of 80–120 μg/kg bd. rhIGF-I therapy has never previously been used in children with Crohn9s disease. We hypothesised that subcutaneous injections of rhIGF-1 would significantly increase circulating IGF-1 concentrations in children with Crohn9s disease induced growth failure, and that twice daily injections would maintain these concentrations. <h3>Methods</h3> Eight children with active Crohn9s disease and growth failure were recruited for an open-label pharmacokinetics study of rhIGF-1 (Increlex). A subcutaneous injection of rhIGF-1 (dose 120 μg/kg) was given, and levels were measured over 24 h. Children were also studied over a second period (5 days) of repeated doses. Blood sugar levels were monitored as hypoglycaemia is a potential adverse effect. Protein losing enteropathy was measured by stool α1-antitrypsin and related to IGF-1 levels attained. <h3>Results</h3> The median age(range) of the children was 12 years(10–14). 4 were female, 4 male, mean (SD) Paediatric Crohn9s Disease Activity Index (PCDAI) was 31.25(14.08). All the children had poor growth (mean growth velocity standard deviation score(SDS) −3.34 (SD 1.13)). All the subjects completed the study. The rhIGF-1 was well tolerated, with only one patient having an (asymptomatic) hypoglycaemic episode. All patients except for one had low baseline IGF-1 levels (mean SDS -1.78 (SD 1.37)) and all showed an increase in 3-h circulating IGF-1 levels following administration of rhIGF-1 (mean SDS 2.70 (SD 3.06)). This increase was significant(p = 0.007). IGF-1 levels were maintained above 0.0 SDS by twice daily injections. This occurred without any change in PCDAI over the 5-day trial period (p = 0.77) Protein-losing enteropathy did not inhibit this response. <h3>Conclusion</h3> Subcutaneous administration of rhIGF-1 significantly increased circulating concentrations of IGF-1 in children with Crohn9s disease-related growth retardation. These results support the initiation of trials to assess the impact of long-term rhIGF replacement therapy on linear growth." @default.
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• W4247387715 date "2011-03-13" @default.
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• W4247387715 title "Subcutaneous rhIGF-1 significantly increases circulating IGF-1 concentrations in children with Crohn's disease induced growth failure" @default.
• W4247387715 doi "https://doi.org/10.1136/gut.2011.239301.35" @default.
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