Background: In Europe, Increlex® (mecasermin) is approved for treatment of growth failure in children with severe primary insulin-like growth factor-1 deficiency (SPIGFD). We present 10-year data (up to October 2018) from the European Increlex® Growth Forum Database (EU-IGFD) registry (NCT00903110) on the frequency, predictive factors, and the potential impact of hypoglycaemia on efficacy outcomes.
Methods: This is an ongoing, multicentre, open-label, observational study monitoring the safety and efficacy of mecasermin in children in clinical practice. Logistic regression analysis was performed to identify predictive factors for hypoglycaemia.
Results: 280 patients were enrolled (safety population, 272 patients; 23 [8.5%] with a previous history of hypoglycaemia). Sixty-four (23.5%) patients experienced at least one hypoglycaemia adverse event (AE; 113 events: 57 verified, 44 suspected, 12 unspecified). Twelve serious hypoglycaemia events occurred in 7 (2.6%) patients. AEs led to withdrawal of 15 (5.5%) patients (3 [1.1%] with hypoglycaemia and 2 [0.7%] with hypoglycaemic unconsciousness). Baseline characteristics of patients who subsequently experienced hypoglycaemia included a lower mean age at first mecasermin injection (8.6 years versus 9.7 years in patients not experiencing hypoglycaemia), more frequent diagnosis of Laron syndrome (31.3% versus 11.1%), and a history of hypoglycaemia events (20.3% versus 4.8%). Laron syndrome and history of hypoglycaemia were found to be predictors for hypoglycaemia (odds ratio [OR] 0.33 [95% confidence interval (CI). 0.16; 0.68], P=0.003 and OR 0.26 [95% CI. 0.10; 0.65], P=0.004, respectively; multivariate analysis). Mean first year mecasermin dose (≤100µg/kg BID versus >100µg/kg BID) was not associated with time to hypoglycaemia (Gehan test: P=0.554). The mean change in height standard deviation score (SDS) from baseline over the first 6 years of mecasermin treatment was similar between patients who did or did not experience hypoglycaemia: changes from baseline at 1, 3 and 6 years were 0.35 (95% CI. 0.21; 0.49), 0.79 (95% CI. 0.53; 1.05) and 0.95 (95% CI. 0.25; 1.66), and 0.33 (95% CI. 0.26; 0.40), 0.78 (95% CI. 0.62; 0.94) and 0.96 (95% CI. 0.67; 1.24), respectively.
Conclusions: Mecasermin may have hypoglycaemic effects. Special attention should be paid to young children, children with a history of hypoglycaemia and those with Laron syndrome. Hypoglycaemia had no impact on the effectiveness of mecasermin in the real-life setting.
19 Sep 2019 - 21 Sep 2019