Background: The EU-IGFD registry comprises data for children with severe primary IGF-I deficiency (SPIGFD) receiving rhIGF-I (mecasermin [rDNA origin] injection; Increlex®) for growth failure.
Objective: To report patient characteristics, effectiveness and safety data for children receiving rhIGF-I for SPIGFD and achieving AH.
Methods: Patients from this ongoing observational study (NCT00903110) were included in analyses if reaching AH (last height velocity [HV] <1 cm/year) by 10-Oct-2017. Population comprised patients discontinuing therapy at AH and those discontinuing for other reasons followed until AH.
Results: Characteristics: Of 247 patients enrolled, 67 achieved AH (43 [64%] male; 27 treatment naïve and prepubertal [NPP]; 40 non-treatment naïve or pubertal [including one undetermined] [NNP]). At baseline, median (Q1Q3) highest stimulated GH levels were 21.35 (13.6040.00) ng/mL. Most patients were pubertal stage 1 (42/64) and had SPIGFD (57/67) including 12 with Laron syndrome. At first rhIGF-I intake in this study, mean (SD) age was 12.9 (2.6) years (NPP, 11.9 [2.1]; NNP, 13.5 [2.8]) and mean (SD) height SDS was 3.73 (1.34) (n=60) (NPP, 3.46 [1.06]; NNP, 3.92 [1.50]). Additionally, HV was 4.47 (1.30) cm/year (n=36), predicted adult height SDS 2.5 (2.2) (n=35) (calculated using: Bayley-Pinneau [19/42], Tanner-Whitehouse [16/42], other [6/42], Roche-Wainer-Thissen [1/42]), weight SDS 2.84 (1.22) (n=60). AH reached was the main reason for treatment discontinuation (39/66: NPP, 15/26; NNP, 24/40), followed by lack of efficacy (9/66). Treatment: Median (Q1Q3): duration was 44.3 (27.954.6) months and dose during last year of treatment was 102.3 (85.8120.0) μg/kg twice daily. Effectiveness: HV improved at year 1 (mean [SD], 6.38 [2.53] cm/year; NPP, 7.11 [2.35]; NNP, 5.91 [2.57]) and remained above baseline level for 23 further years. Final adult height SDS: mean (SD), 3.08 (1.79) (NPP: 2.30 [1.35]; NNP: 3.62 [1.88]). Difference between final and baseline height SDS: mean (SD), 0.7 (1.0) (NPP: 1.1 [0.7]; NNP: 0.4 [1.0]). For NPP, lower baseline age predicted greater changes from baseline in final adult height SDS (multivariate analysis [estimate (95% CI) by 1-unit increment: 0.25 (0.130.36); P<0.001]). Safety: 32/67 patients reported targeted adverse events (most frequent: hypoglycaemia [13/67]).
Conclusions: Patients achieving AH were 12.9 years old at rhIGF-I treatment initiation. Nevertheless, rhIGF-I improved adult height in SPIGFD, with greater improvements for NPP than NNP patients. Age was a predictor for change from baseline in final adult height SDS. Safety is consistent with the known profile of mecasermin.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology