ESPE Abstracts

Background: Severe primary insulin-like growth factor-1 deficiency (SPIGFD) is a rare condition for which replacement therapy with recombinant human insulin-like growth factor-1 (rhIGF 1; mecasermin [Increlex^®]) is approved for treatment in Europe and the USA. SPIGFD is defined as a height standard deviation score (HtSDS) ≤-3, and baseline IGF-1 <2.5th percentile (European indication) or ≤-3 SDS (USA indication) for age and gender, despite sufficient levels of growth hormone (GH; cutoff not defined). Differences in diagnostic workup for children may vary across geographies, depending on national reimbursement and genetic diagnosis policies.

Methods: The registry is an ongoing, multicentre, open-label, observational study monitoring safety and effectiveness of mecasermin in children/adolescents with SPIGFD (NCT00903110) in eight European countries and the USA (data not yet included). Eligible patients: aged 2–18 years, receiving mecasermin. This analysis describes clinical practices in real-life settings across Europe to assess SPIGFD diagnosis from data collected in the registry from December 2008–October 2021.

Results: At the time of data cut-off (4 October 2021), 259/306 patients enrolled in the registry were reported as diagnosed with SPIGFD. HtSDS based on local height charts and baseline IGF-1 was reported in 90.3% (n=234) and 92.7% (n=240) of patients with SPIGFD, respectively. Random GH and GH peak were reported in 68.7% (n=177) and 64.9% (n=168) of patients, respectively. Additionally, baseline IGF binding protein-3 (IGFBP-3) was reported in 69.1% (n=179) of patients and baseline GH binding protein (GHBP) was tested in four patients, none of whom presented with Laron syndrome. IGF-1 generation was reported in 43.2% (n=112) of patients with SPIGFD, and at least one genetic test was reported in 56.3% (n=144). The DPC/Immulite kit was the most frequently used IGF-1 assay (48.0%; n=71/148; median [min; max]: 65.0 [<1; 562] ng/mL). Between countries, proportion of patients with reported IGF-1 generation testing ranged from 18.8% (n=9/48) in France to 100% (n=21/21) in Poland, and the performance of at least one genetic test ranged from 19.0% in Poland (n=4/21), to 81.5% in Italy (n=22/27).

Conclusions: In children reported to have SPIGFD enrolled in the registry, HtSDS and baseline IGF-1 were reported in >90% of patients, while additional biochemical information including GH levels were less frequently reported, indicating that full reporting should be pursued. Recommendations on SPIGFD recognition and diagnosis should be produced and made available to the medical community in order to improve homogeneity in the diagnostic workup of these patients across countries.