Register of Patients Treated with Growth Hormone (REPAR): Data Analysis as a Path to Further Optimization of Care

Data Processing Methodology

In the first part of the project, data from Czech patients were transferred to REPAR from the KIGS (n = 1204), ECOS (n = 194), and NordiNet IOS (n = 1205) databases; a total of 2603 children treated with growth hormone. Additionally, data from the GeNeSIS database (n = 344) were continuously included. In the prospective part of the project, which aims to include newly treated patients, 1727 patients have been added to REPAR.

The total of 4330 patients in the database can be divided into several indication groups:

• growth hormone deficiency (GHD)
• Turner syndrome (TS)
• chronic renal insufficiency (CRI)
• postnatal growth failure following intrauterine growth restriction (SGA)
• Prader-Willi syndrome (PWS)
• SHOX deficiency
• heterogeneous group labeled as “other diagnosis”

The entered data include basic demographic information, initial examination (height, weight, sexual maturation, bone age, IGF-1 level, results of growth hormone secretion stimulation tests, and genetic examination results), parental height data, perinatal data, indication for rhGH treatment, treatment start date, and rhGH dose. Follow-up visits are updated at six-month intervals. The last part of the record is the end of treatment or observation and the reasons for it.

Results

Growth hormone dosing (GH) varies depending on the diagnosis and nature of treatment (substitutive or therapeutic). Overall, the dose ranges between 0.020 and 0.046 mg/kg/day (5th and 95th percentile). The lowest dose per kg of body weight is administered to PWS patients (0.025 mg/kg/day [0.009−0.038; 5th and 95th percentile]), and the highest to CRI patients (0.045 mg/kg/day [0.028−0.060; 5th and 95th percentile]).

The lowest age at treatment initiation is recorded in PWS patients (1.5 years in boys; 95% confidence interval [CI] 1.0−1.9 and 1.3 years in girls; 95% CI 0.7−2.0). The highest age at therapy initiation was in boys with CRI (8.0 years; 95% CI 2.2−13.9) and in girls with SHOX deficiency (8.3 years; 95% CI 7.3−9.4). Treatment of GHD, TS, and SGA patients typically begins between the ages of 6 and 8 on average.

Discussion

Differences in the daily dose are due to the varying needs of individual indication groups. Higher doses in pharmacological treatments ensure overcoming resistance to physiological GH levels, allowing for improved growth response. Early initiation of therapy significantly enhances growth prognosis and psychosocial development, thereby achieving a higher quality of life for the patient. Early treatment of children with growth disorders is made possible by more precise and faster molecular diagnostics, which are now available.

The trend of age at initiation of GHD, PWS, and Turner syndrome therapy shows a statistically significant decreasing trend. This reflects, among other things, the fact that in the years when the patients included in the registry were diagnosed, growth hormone therapy for these diagnoses was not available. The groups of patients with SHOX deficiency and CRI are not very numerous, thus the decreasing trend is not statistically significant here.

Final height prediction is determined based on gender and the adjusted mid-parental height, but also reflects the nature of the disorder, compliance, and adherence to therapy. Results are gradually improving thanks to optimization of treatment for the given indication groups. 

Conclusion

The REPAR register collects data on pediatric patients treated with rhGH in the Czech Republic and contributes to the long-term optimization of care for children with growth disorders. Data analysis provides the opportunity for both individual and group evaluation of therapy data for each indication group. The results can also serve to further understand the effects of GH, predict therapy success, and conduct pharmacoeconomic assessments. The epidemiological significance of the database lies in the possibility of researching the incidence and prevalence of growth disorders in children. 

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Source: Kodytková A., Al Lababidi E., Čermáková I. et al. Analysis of data from the national register of patients treated with growth hormone REPAR. Česko-slovenská pediatrie 2020; 75 (4): 205−212.