Abstract
ObjectiveThe European Increlex® Growth Forum Database Registry monitors the effectiveness and safety of recombinant human insulin-like growth factor-1 (rhIGF1; mecasermin, Increlex®) therapy in patients with severe primary IGF1 deficiency (SPIGFD). We present data from patients with and without a reported genetic diagnosis of Laron syndrome (LS).DesignOngoing, open-label, observational registry (NCT00903110).MethodsChildren and adolescents receiving rhIGF1 therapy from 10 European countries were enrolled in 2008–2017 (n = 242). The treatment-naïve/prepubertal (NPP) cohort (n = 138) was divided into subgroups based on reported genetic diagnosis of LS (n = 21) or non-LS (n = 117). Multivariate analysis of the NPP-non-LS subgroup was conducted to identify factors predictive of growth response (first-year-height standard deviation score (SDS) gain ≥ 0.3). Assessments included change in height and weight over 5 years and adverse events (AEs).ResultsHeight SDS gain from baseline was greater in the NPP-LS than the NPP-non-LS subgroup after 1 years’ treatment (P < 0.05). In the NPP-non-LS subgroup, 56% were responders; young age at baseline was a positive independent predictive factor (P < 0.001). NPP-non-LS-responders and the NPP-LS subgroup had a similar mean age (6.07 years vs 7.00 years) at baseline and height SDS gain in year 1 (0.64 vs 0.70), although NPP-non-LS-responders were taller (P < 0.001) at baseline. BMI SDS changes did not differ across subgroups. Treatment-emergent AEs were experienced by 65.3% of patients; hypoglycaemia was most common.ConclusionsIn most NPP children with SPIGFD, with or without LS, rhIGF1 therapy promotes linear growth. The safety profile was consistent with previous studies.
Highlights
Severe primary insulin-like growth factor deficiency (SPIGFD) is associated with postnatal growth failure (1)
246 patients enrolled in the European Increlex® Growth Forum Database (Eu-IGFD) Registry from December 2008 to May 2017, and 138 were included in the NPP cohort analyses; with Laron syndrome (LS) (n = 21), or without LS (n = 117; Fig. 1)
The non-NPP cohort baseline characteristics, puberty and previous treatment status, recombinant human insulin-like growth factor-1 (rhIGF1) therapy dosing and changes in height SDS, height velocity, BMI SDS and weight SDS are provided in Supplementary materials (Supplementary Tables [1, 2, 3, 4, 5] and 6, see section on supplementary materials given at the end of this article)
Summary
Severe primary insulin-like growth factor deficiency (SPIGFD) is associated with postnatal growth failure (1). It is characterised by very low levels of insulin-like growth factor-1 (IGF1) and other growth hormone (GH)-regulated proteins, despite normal or elevated GH secretion (2, 3). In patients with Laron syndrome (LS), SPIGFD results from a mutation in the GH receptor gene, causing GH insensitivity and severe-to-extreme short stature (–4 to –10 height standard deviation score (SDS), increasing with age) (2, 3). In addition to proportionate short stature, phenotypic characteristics of LS include frontal bossing, hypoplastic midface, central obesity, small genitalia and delayed puberty (4, 5). Most patients with severe growth stunting and biochemical characteristics of SPIGFD cannot be assigned a causative genetic diagnosis (8)
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