Real-world outcomes can differ from those seen in tightly-controlled clinical trials, so researchers wanted to examine the patterns of growth hormone treatment in a large cohort of children in Israel.
A recent study from Israel examined a decade of growth hormone (GH) treatment patterns and outcomes in a real-world setting and found that who gets treated for GH issues is skewed in terms of socioeconomic (SES) background.
Randomized controlled trials have demonstrated short-term efficacy and safety of GH therapy, but outcomes in the real world can be much different, noted the authors in Frontiers in Pediatrics, including knowing the trajectory to adult height.
Available research suggests that success of GH therapy depends the age treatment is started, how well families adhere to therapy, the indication, and gender. The 2 most common reasons for GH therapy are GH deficiency (GHD) and idiopathic short stature (ISS). Other indications are Turner syndrome (TS), Prader-Willi syndrome (PWS), chronic renal failure (CRF), small for gestational age (SGA), and Noonan's syndrome.
This large retrospective database study included data on 2379 children initiating GH treatment in Maccabi Healthcare Services (MHS) between January 2004 and December 2014. The MHS database includes up to 20 years of data on 2 million members and represents a sample of 25% of the Israeli population.
The database integrates data from the patients' electronic medical records (EMR), which includes growth parameters, the indication for treatment, and socioeconomic factors.
The objectives of the study were to evaluate prescribing patterns, adherence, and outcomes of GH therapy in patients followed from the start of treatment and for at least 12 months.
Most patients starting GH treatment were male (62.1%) with a mean [SD] age of 9.8 [3.1] years. The height standard deviation score (SDS) was −2.36 [0.65] and time from short stature diagnosis to first GH purchase was 4.8 [3.3] years.
Findings also showed that ISS represented the majority of diagnoses that led to GH treatment (n = 1615, or nearly 68%) and GHD made up 611 cases, or 25.7%.
The mean treatment period was 3.5 [0.95] years and nearly 80% of children were treated for more than 3 years.
After 3 years, mean height gain SDS was 1.09 [0.91] for GHD and 0.96 [0.57] for ISS (P = .0004).
Adult height (age 15 for girls and 17 for boys) was recorded for 624 patients (26.2%) with better outcomes for GHD than ISS (−1.0 [0.82] vs. −1.28 [0.93], respectively; P = .0002).
Good adherence with therapy, assessed during follow-up, was defined as the proportion of days covered (PDC) >80%. Adherence declined over time, the investigators found. A little more than 78% of the group had good adherence during the first year; the rate fell to 68.1% during the third year of the treatment.
Recombinant GH therapy during this study took the form of daily injections, and since adherence was defined as PDC, it could not take into account the possibility of parents or guardians not giving the injection some days.
Interestingly, most of the patients came from high socioeconomic (SES) backgrounds (61.3% for ISS and 59.7% for GHD). This differed from the general pediatric population in the MHS, where 23% belongs to the highest SES tertile and 14.4% belongs to the lowest.
GH treatment is tilted when it comes to SES levels, the authors said, and it is unlikely to be solely due to issues of cost, since the cost of the treatment in Israel is largely subsidized by health maintenance organizations.
Previous studies have indicated that parents seeking evaluation and treatment for short stature in their children tend to have higher education levels and income, and that “referral decisions are strongly influenced by the level of parental concern and physician attitudes,” the researchers noted.
Clinicians should be aware that issues with GH deficiencies may be underrecognized in patients from lower SES tertiles, they said.
The strengths of the study included the fact that it relied on high-quality, standardized data with a large sample size and long follow-up period.
“Appropriate referral, diagnosis, and follow-up care may result in better treatment outcomes with GH therapy,” the researchers said.
Ben-Ari T, Chodick G, Shalev V, Goldstein D, Gomez R, Landau Z. Real-world treatment patterns and outcomes of growth hormone treatment among children in israel over the past decade (2004–2015). Front Pediatr. Published online August 20, 2021. doi: 10.3389/fped.2021.711979