title: Dose-sparing and safety-enhancing effects of an IGF-I-based dosing regimen in short children treated with growth hormone in a 2-year randomized controlled trial: therapeutic and pharmacoeconomic considerations.
abstract: OBJECTIVE
  Titrating the dosage of growth hormone (GH) to serum levels of insulin-like growth factor-I (IGF-I) is a feasible treatment strategy in children with GH deficiency (GHD) and idiopathic short stature (ISS). The objective was to assess the dose-sparing effect and theoretical safety of IGF-I-based GH therapy.
  
  
  METHODS
  This was a post hoc analysis of a previously described 2-year, multicenter, open-label, randomized, outpatient, controlled clinical trial in 172 prepubertal short children [age 7·5 ± 2·4 years; height standard deviation score (HSDS) -2·64 ± 0·61] classified by baseline peak GH levels as GHD (<7 ng/ml) or ISS (≥7 ng/ml).
  
  
  METHODS
  Conventional weight-based dosing of GH (0·04 mg/kg/day) (n = 34) or GH dosing titrated to an IGF-I target of 0 SDS (IGF0T; n = 70) or an IGF-I target of +2 SDS (IGF2T; n = 68).
  
  
  METHODS
  Change in HSDS per GH mg/kg/day dose (∆HSDS/GH dose ratio) and proportion of IGF-I levels above +2 SDS at the end of 2 years.
  
  
  RESULTS
  GH dosing titrated to an IGF-I target of 0 SDS was the most dose-sparing treatment regimen for GHD or ISS children (mean±SE ∆HSDS/GH dose ratios 48·1 ± 4·4 and 32·5 ± 2·8, respectively) compared with conventional dosing (30·3 ± 6·6 and 21·3 ± 3·5, respectively; P = 0·02, P = 0·005) and IGF2T (32·7 ± 4·8 and 16·3 ± 2·8, respectively; P = 0·02, P < 0·0001). IGF0T also resulted in the fewest IGF-I excursions above +2 SDS (6·8% vs 30·0% for conventional dosing; P < 0·01).
  
  
  CONCLUSIONS
  IGF-I-based GH dosing, targeted to age- and gender-adjusted means, may offer a more dose-sparing and potentially safer mode of therapy than traditional weight-based dosing.
authors.affiliation: University of Southern California, Los Angeles, CA, USA.
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.forename: Wayne
authors.initials: W
authors.lastname: Weng
authors.forename: Alan D
authors.initials: AD
authors.lastname: Rogol
authors.forename: Ron G
authors.initials: RG
authors.lastname: Rosenfeld
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Kappelgaard
authors.forename: John
authors.initials: J
authors.lastname: Germak
mesh_terms: D001827:Body Height / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004393:Dwarfism, Pituitary / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male
chemical_list: D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone