Effect of adherence to growth hormone treatment on 0–2 year catch-up growth in children with growth hormone deficiency

Abstract

BackgroundQuantifying the association between adherence and the growth response to growth hormone (GH) treatment is hampered by suboptimal methods of measuring adherence, confounders associated with the growth response, and restriction of the outcome parameters to yearly growth velocities.AimTo investigate the effect of adherence on the two-year growth response to GH treatment in prepubertal children with idiopathic isolated growth hormone deficiency (GHD) participating in the easypod connect observational study (ECOS), a 5-year, Phase IV open-label study to continuously assess real-world adherence via the easypod electronic drug-delivery device.Patients and methodsOutcome measures were change in height standard deviation score (ΔHSDS), index of responsiveness (IoR), and parameters of two catch-up growth (CUG) curve functions (monomolecular growth curve and second degree polynomial) with adj-HSDS (HSDS minus Target height (TH) SDS) as dependent variable. Inclusion criteria were GHD, naïve to GH treatment, known TH, age <10y in girls and <12y in boys, ≥3 measurements, HSDS <-2 at start, complete data on growth and adherence in the first and second year. Linear regression analyses were performed to test the association between adherence (continuous and high vs. low) and the outcome measures, also adjusted for potential clinical confounders (age at start, adj-HSDS at start, birth weight SDS, gestational age (<37 weeks vs ≥37 weeks), GH dose, GH max (n = 58)). The formula of IoR already adjusts for confounders.ResultsIn total, 95 patients complied with the inclusion criteria. The strongest associations were found between high adherence in the second year (≥91% as cut-off value) and IoR 2y (+0.62), and average adherence and high adherence (≥78%) in the first two years and ΔHSDS 0-2y (+0.11 SD per 1 injection/week, and +0.34 SD for high vs. low adherence).ConclusionSuboptimal adherence negatively affected the growth response in the first two years of GH treatment.

Adherence to treatment in children with growth hormone deficiency, small for gestational age and Turner syndrome in Mexico: results of the Easypod™ connect observational study (ECOS)

“…The global ECOS study found a positive correlation between adherence and attainment of growth milestones [6]. Contrary to previous reports [5,13], here, we found a significant correlation between adherence and growth outcomes at 1-year after initiating r-hGH therapy with Easypod™. This difference among ECOS subpopulations may be due to sample size differences as well as the proportions of r-hGH therapy indications, which may lead to potential differences in the magnitude of clinical response.…”

“…The human recombinant growth hormone (h-rGH) is indicated to treat clinical conditions that imply short stature, such as GH deficiency (GHD), children born small for gestational age (SGA) who failed to show catch-up growth and Turner syndrome (TS), among other medical conditions [1][2][3][4][5][6]. Adherence to h-rGH is one of the most important factors that determine achievement of clinical targets [7−10].…”

Managing Paediatric Growth Disorders: Integrating Technology Into a Personalised Approach

“…Its application to the treatment of growth disorders is more challenging because therapy is geared to long-term responses and benefits, rather than short-term metabolic control. However, one area where digital technology has been effective is in the electronic monitoring of GH injections ( 13 , 14 ). The use of an electromechanical auto-injector, which records every injection that is given and communicates the data both to the patient and the HCP, is a major advance ( 15 ).…”

Growth Hormone Therapy for Paediatric Growth Disorders: The Past, Present, and Future

“…The difference between observed and predicted gain in height or height velocity can be a measure of the adherence to the hGH treatment regimen. If responsive reduced while the diagnosis is correct and the presence of intercurrent disease is ruled out, poor adherence to the hGH regimen should be considered [45,46]. Monitoring of adherence should begin as the hGH treatment is initiated because some patients may not be compliant from the start or not renew their prescriptions, particularly if the evidence of real benefit is lacking [47][48][49].…”

“…Electronic monitoring of GH injections can be performed using the easypod injection device and Easypod Connect system, which is the only such device currently approved [45]. The device facilitates administration of a preset dose of hGH, records injection times and doses, and provides the patient with information such as number of doses remaining [53].…”