ESPE Abstracts

Background & Objective: Recombinant human insulin like growth factor 1 (rhIGF1) therapy is the only treatment available for primary IGF1 deficiency and related disorders. However, it’s efficacy in promoting growth is controversial and needs cautious monitoring for adverse effects. The aim of this study was to determine the long-term efficacy and safety profile of rhIGF1 therapy.

Methods: Retrospective review of all patients on rhIGF1 therapy over the last 13 years (2008 -2021) at a single tertiary centre.

Results: Eleven patients (8 male) on rhIGF1 therapy were identified. Seven harboured genetic mutations: GH receptor gene mutation (3/7), STAT5B (2/7), STAT1 (1/7), GH1 gene deletion (1/7). Four had no identified mutation but were GH insensitive. Seven patients had an escalating IGF-1 generation test with no significant response. Median age at presentation was 3.7 (1.57- 13.97) years and median age at start of treatment was 4.12 (2- 22.9) years. Starting dose of rhIGF1 was 77-85 mcg/kg/day (mean = 79.89 mcg/kg/day) which was gradually increased to 151- 242 mcg/kg/day (mean = 206 mcg/kg/day). Post-treatment follow-up ranged from 1.3 to 12.5 years. Mean pre-treatment height velocity (HV) was 3.33 (0.85-6.47) cm/year. All cases showed post-treatment HV increment. Maximum HV was seen at 1-year post-treatment (7.54cm/year), followed by 6.13cm/year at 2 years, 5.7cm/year at 3 years, 5.8cm/year at 4 years, and 5cm/year at 6 years. The group with known genetic mutations showed a higher mean 1-year post-treatment HV (8.49 cm/year) as compared to the group with no identified mutation (4.11cm/year). Mean pre-treatment height was -4.60 (-2.66 to -7.31) SD. Post-treatment height improved to -3.11 (-1.85 to -4.33) SD. Hypoglycaemia was observed in 9/11 patients. 4/9 patients developed hypoglycaemia after the first dose and needed overnight feeding via gastrostomy, with good effect. Three of these patients had a genetic mutation and showed the best response to rhIGF1 (HV 9.95(7.25-11.8) cm/year). Five patients developed hypoglycaemia after increasing IGF-1 dose and needed dose reduction with or without cornstarch and overnight feeds. Three patients developed tonsillar hypertrophy (OSA) within 4-10 months post-treatment (2 needed tonsillectomy). One patient developed left ventricular hypertrophy 2-years post-treatment. No patients developed benign intracranial hypertension.

Conclusion: Recombinant IGF1 therapy promotes growth in primary IGF1 deficiency, especially in patients with known underlying genetic mutations. Hypoglycaemia is the most common adverse effect, and its severity is associated with the response to rhIGF1 therapy. Gastrostomy feeds were highly effective at preventing hypoglycaemia.