Safety Outcomes and Near-Adult Height Gain of Growth Hormone-Treated Children with SHOX Deficiency: Data from an Observational Study and a Clinical Trial

Abstract

Background/Aims: To assess auxological and safety data for growth hormone (GH)-treated children with SHOX deficiency. Methods: Data were examined for GH-treated SHOX-deficient children (n = 521) from the observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS). For patients with near-adult height information, GeNeSIS results (n = 90) were compared with a clinical trial (n = 28) of SHOX-deficient patients. Near-adult height was expressed as standard deviation score (SDS) for chronological age, potentially increasing the observed effect of treatment. Results: Most SHOX-deficient patients in GeNeSIS had diagnoses of Leri-Weill syndrome (n = 292) or non-syndromic short stature (n = 228). For GeNeSIS patients with near-adult height data, mean age at GH treatment start was 11.0 years, treatment duration 4.4 years, and height SDS gain 0.83 (95% confidence interval 0.49-1.17). Respective ages, GH treatment durations and height SDS gains for GeNeSIS patients prepubertal at baseline (n = 42) were 9.2 years, 6.0 years and 1.19 (0.76-1.62), and for the clinical trial cohort they were 9.2 years, 6.0 years and 1.25 (0.92-1.58). No new GH-related safety concerns were identified. Conclusion: Patients with SHOX deficiency who had started GH treatment before puberty in routine clinical practice had a similar height gain to that of patients in the clinical trial on which approval for the indication was based, with no new safety concerns.

SHOX haploinsufficiency presenting with isolated short long bones in the second and third trimester

“…Administration of recombinant human growth hormone by daily subcutaneous injections is a safe and effective therapeutic option for patients with short stature secondary to SHOX deficiency [39][40][41]. In a prospective multicentre study with longitudinal follow-up, 57% of patients with SHOX deficiency treated with recombinant human growth hormone attained a final height within the population reference range; similar figures were observed among SHOX-deficient patients treated in routine clinical practice [22,40].…”

“…Although longitudinal studies have suggested that failure of linear growth in SHOX haploinsufficiency is measureable from an early age, SHOX deficiency is rarely diagnosed before late childhood [9,10,21]. Recombinant growth hormone administered by daily subcutaneous injection is a safe and effective treatment for growth failure in SHOX haploinsufficiency [22].…”

Growth hormone treatment of Canadian children: results from the GeNeSIS phase IV prospective observational study

“…This gain was consistent with the results from the Canadian randomized clinical trial and other studies of growth hormone treatment in Turner syndrome. 4,5,38 The tendency of Canadian physicians to treat shorter patients with Turner syndrome may reflect parent/ patient health care priorities, 37 although the impact of provincial funding decisions may also play a role.…”

Growth hormone prescribing patterns in the UK, 2013–2016

“…Although the male to female ratio was 1:1 for the SHOXd group in our audit, the numbers were small. Other studies with larger cohorts have reported no differences in gender distribution18 19 or a greater proportion of girls 20. One explanation for these variations is ascertainment bias owing to the relatively overt phenotype in girls and underdiagnosis in boys with SHOXd.…”