Safety and Efficacy of Pediatric Growth Hormone Therapy: Results From the Full KIGS Cohort

Abstract

Context: The Kabi/Pfizer International Growth Database (KIGS) is a large, international database (1987-2012) of children treated with recombinant human growth hormone (rhGH) in real-world settings.

Objective: This work aimed to evaluate the safety and efficacy of rhGH from the full KIGS cohort.

Methods: Data were collected by investigators from children with growth disorders treated with rhGH (Genotropin [somatropin]; Pfizer). Safety was evaluated in all treated patients, and efficacy in those treated for 1 year or more. A subgroup included patients treated for 5 years or more (≥ 2 years prepubertal) who had reached near-adult height (NAH). Main outcomes included adverse events (AEs), serious AEs (SAEs), and height growth.

Results: The full KIGS cohort (N = 83 803 [58% male]) was treated for idiopathic GH deficiency (IGHD; 46.9%), organic GHD (10.0%), small for gestational age (SGA; 9.5%), Turner syndrome (TS; 9.2%), idiopathic short stature (ISS; 8.2%), and others (16.2%). Median rhGH treatment duration was 2.7 years and observation 3.1 years. SAEs occurred in 3.7% of patients and death in 0.4%. The most common SAEs were recurrence of craniopharyngioma (n = 151), neoplasm (n = 99), and cancer (n = 91); and scoliosis (n = 91). Median first-year delta height-SD score (SDS) (Prader) in prepubertal patients was 0.66 (IGHD), 0.55 (ISS), 0.58 (TS), and 0.71 (SGA). Median gains in NAH-SDS were 1.79 (IGHD), 1.37 (ISS), and 1.34 (SGA) for boys, and 2.07 (IGHD), 1.62 (ISS), 1.07 (TS), and 1.57 (SGA) for girls.

Conclusion: Data from KIGS, the largest and longest running international database of rhGH-treated children, show that rhGH is safe and increases short-term height gain and adult height across GHD and non-GHD conditions.

Keywords: KIGS; children; efficacy; growth hormone; safety; short stature.

Figure 1.

Patient disposition and main analysis cohorts. Baseline prepubertal percentages were based on the number of patients with available puberty status data; n = 72 355; 23 246; 49 109; and 7911 for the safety, excluded, efficacy, and NAH sets, respectively. KIGS, Kabi/Pfizer International Growth Database; NAH, near adult height; rhGH, recombinant human growth hormone.

Figure 2.

SAE frequency in the safety cohort by type of disorder (MedDRA SOC). Related SAEs are SAEs considered to be related to rhGH treatment based on investigators’ opinion without central adjudication. General/admin sites includes general disorders that affect several body systems or sites and administration site conditions. Investigations include adverse events based on results from clinical laboratory tests, radiologic tests, physical examinations, and physiologic tests; only MedDRA PTs representing investigation procedures and qualitative results are in this SOC. Neoplasms include benign, malignant, and unspecified neoplasms. admin, administration; MedDRA, Medical Dictionary for Regulatory Activities; PT, preferred term; rhGH, recombinant human growth hormone; SAE, serious adverse event; SOC, system organ class.

Figure 3.

Growth outcomes in the NAH subgroup (data from girls and boys combined). A, Height-SDS. B, Changes in height-SDS vs start of rhGH treatment. C, Height velocity-SDS. D, BMI-SDS. E, Difference between height-SDS and MPH-SDS. F, Percentage of patients achieving an NAH within the range of MPH ± 1.5 SDS. BMI, body mass index; congGHD, congenital GHD; CP, craniopharyngioma; CRF, chronic renal failure; Diff-SDS, height SDS minus mid-parental SDS; ECM, extracranial malignancy; GHD, growth hormone deficiency; Ht-SDS, height-SDS; HtV, height velocity; IGHD, idiopathic GHD; ISS, idiopathic short stature; MB, medulloblastoma; NAH, near-adult height; NSD, neurosecretory dysfunction; OCT, other cranial tumors; OS, other syndromes; PWS, Prader-Willi syndrome; rhGH, recombinant human growth hormone; SDS, SD score; SGA, small for gestational age; TS, Turner syndrome. SDS was calculated based on Prader references (20) for height and the reference by Cole et al (21) for BMI.