Supplementary Material for: Adult and Near-Adult Height in Patients with Severe Insulin-Like Growth Factor-I Deficiency after Long-Term Therapy with Recombinant Human Insulin-Like Growth Factor-I

<b><i>Background:</i></b> Treatment with recombinant human insulin-like growth factor-I (IGF-I) stimulates linear growth in children with severe IGF-I deficiency (IGFD). <b><i>Aims:</i></b> To evaluate the efficacy and safety of treatment with IGF-I in patients with severe IGFD treated until adult or near-adult height. <b><i>Methods:</i></b> Twenty-one children with severe IGFD were treated until adult or near-adult height under a predominantly open-label design. All patients were naive to IGF-I. Recombinant human IGF-I was administered subcutaneously in doses between 60 and 120 µg/kg twice daily. Nine patients received additional therapy with gonadotropin- releasing hormone (GnRH) analog for a mean period of 2.9 ± 1.8 years. <b><i>Results:</i></b> Mean duration of treatment was 10.0 years. Mean height velocity increased from 3.1 cm/year prior to treatment to 7.4 cm/year during the first year of treatment. Height velocities during the subsequent years were lower, but remained above baseline for up to 12 years. Cumulative mean Δ height SD score at (near) adult height was +2. The observed mean gain in height was 13.4 cm more than had been expected without treatment. The adult height achieved by the patients also treated with GnRH analog was not different from those who received IGF-I therapy alone. There were no new safety signals identified in these patients, a subset of those previously reported. <b><i>Conclusion:</i></b> Long-term therapy with IGF-I improves adult height of patients with severe IGFD. Most patients did not bring their heights into the normal adult range

Supplementary Material for: Recombinant Human Growth Hormone Plus Recombinant Human Insulin-Like Growth Factor-1 Coadministration Therapy in Short Children with Low Insulin-Like Growth Factor-1 and Growth Hormone Sufficiency: Results from a Randomized, Multicenter, Open-Label, Parallel-Group, Active Treatment-Controlled Trial

<b><i>Background/Aims:</i></b> Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) both contribute to growth. To determine if recombinant human (rh)GH + rhIGF-1 therapy is more effective than rhGH alone to treat short stature, we assessed the efficacy and safety of coadministered rhGH + rhIGF-1 in short children with GH sufficiency and low IGF-1. <b><i>Methods:</i></b> In a 3-year, randomized, multicenter, open-label trial, patients with height SD score ≤−2.0 and IGF-1 SD score ≤−1.0 for age and sex, and with stimulated GH ≥10 ng/ml for age and sex, were randomized to receive (all doses in µg/kg/day): 45 rhGH alone (group A), 45 rhGH + 50 rhIGF-1 (group B), 45 rhGH + 100 rhIGF-1 (group C) or 45 rhGH + 150 rhIGF-1 (group D). Height velocity (HV) and Δ height SD score were measured. <b><i>Results:</i></b> The first-year HV (modified intention-to-treat population) was 9.3 ± 1.7 cm/year (group A), 10.1 ± 1.3 cm/year (group B), 9.7 ± 2.5 cm/year (group C) and 11.2 ± 2.1 cm/year (group D) (p = 0.001 for groups A vs. D). This effect was sustained, resulting in a height SD score improvement during the second and third years. Most treatment-emergent adverse events were mild and transient. <b><i>Conclusion:</i></b> In children with short stature, GH sufficiency and low IGF-1, coadministration of rhGH/rhIGF-1 (45/150 µg/kg) significantly accelerated linear growth compared with rhGH alone, with a safety profile similar to the individual monotherapies