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. (7th February 2014)

• Record Type: Journal Article
• Authors: Cohen, Pinchas; Weng, Wayne; Rogol, Alan D.; Rosenfeld, Ron G.; Kappelgaard, Anne‐Marie; Germak, John
• Is Part Of: Clinical endocrinology. Volume 81:Number 1(2014:Jul.)
• Page Start: 71
• Page End: 76
• Publication Date: 2014-02-07
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12408
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12408-abs-0001"> <title>Summary</title> <sec id="cen12408-sec-0001" sec-type="section"> <title>Context and objective</title> <p>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.</p> </sec> <sec id="cen12408-sec-0002" sec-type="section"> <title>Design, setting and patients</title> <p>This was a <italic>post hoc</italic> 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).</p> </sec> <sec id="cen12408-sec-0003" sec-type="section"> <title>Intervention</title> <p>Conventional weight‐based dosing of GH (0·04 mg/kg/day) (<italic>n</italic> = 34) or GH dosing titrated to an IGF‐I target of 0 SDS (IGF0T; <italic>n</italic> = 70) or an IGF‐I target of +2 SDS (IGF2T; <italic>n</italic> = 68).</p> </sec> <sec id="cen12408-sec-0004" sec-type="section"> <title>Main Outcome Measures</title> <p>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.</p> </sec> <sec id="cen12408-sec-0005" sec-type="section"> <title>Results</title> <p>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; <italic>P </italic>=<italic> </italic>0·02, <italic>P </italic>=<italic> </italic>0·005) and IGF2T (32·7 ± 4·8 and 16·3 ± 2·8, respectively; <italic>P </italic>=<italic> </italic>0·02, <italic>P </italic><<italic> </italic>0·0001). IGF0T also resulted in the fewest IGF‐I excursions above +2 SDS (6·8% <italic>vs</italic> 30·0% for conventional dosing; <italic>P </italic><<italic> </italic>0·01).</p> </sec> <sec id="cen12408-sec-0006" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>