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

Summary Context and 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. Design, setting and patients 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 ). Intervention 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 ( IGF 0T; n  = 70) or an IGF ‐I target of +2 SDS ( IGF 2T; n  = 68). Main Outcome Measures 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 IGF 2T (32·7 ± 4·8 and 16·3 ± 2·8, respectively; P  =   0·02, P  <   0·0001). IGF 0T 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.