title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pediatric Endocrinology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Philippe F
authors.initials: PF
authors.lastname: Backeljauw
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Miller
authors.forename: Pascale
authors.initials: P
authors.lastname: Dutailly
authors.forename: Aude
authors.initials: A
authors.lastname: Houchard
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lawson
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Hale
authors.forename: Barry
authors.initials: B
authors.lastname: Reiner
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sperling
mesh_terms: D001827:Body Height / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I