medwireNews: Findings from the PATRO Children study support the use of a biosimilar formulation of recombinant human growth hormone (rhGH; somatropin) in children with Turner’s syndrome (TS).
The postmarketing surveillance study “demonstrates that treatment with biosimilar rhGH […] is well tolerated and effective in TS patients managed in real-life clinical practice”, report Hichem Zouater, from Sandoz GmbH in Holzkirchen, Germany, and co-workers.
The team reviewed the medical records of 348 TS patients who began treatment with the biosimilar rhGH at one of 130 centres in Europe, Australia, Canada and the USA.
At baseline, the majority (81.6%) of patients were naïve to rhGH therapy, while 18.4% had received an average 51.4 months of rhGH therapy before entering the study. In all, 90.2% of the patients were prepubertal, with average ages of 8.2 years for treatment-naïve and 9.8 years for pretreated participants.
The treatment-naïve and pretreated participants received an average baseline daily dose of 38.5 and 43.2 µg/kg, respectively, rising to daily averages of 44.1 and 45.1 µg/kg after 1.0–1.5 years of treatment.
Only 22.2% of treatment-naïve and 20.3% of pretreated patients began treatment with a daily dose of 45–50 µg/kg as recommended in the 2017 clinical practice guidelines, Zouater and co-authors note in Hormone Research in Paediatrics.
“This is important, as the greatest effect on growth response is observed during the first year of treatment”, the researchers emphasize.
“These findings suggest that guideline-recommended rhGH doses may not always be closely adhered to in routine clinical practice”, they say, but acknowledge “that patients with TS in PATRO Children will likely have started rhGH treatment before the updated guidelines were published in 2017.”
Efficacy analysis was conducted in the 163 patients who completed at least 3 years of treatment. Of the 131 treatment-naïve patients in this group, 98.5% were prepubertal at baseline, as were 90.6% of the 32 pretreated children.
The mean gain in height standard deviation score (SDS) from baseline to year 3 was +1.17 for the prepubertal treatment-naïve patients, and +0.04 for the prepubertal patients who had previously received rhGH.
Adult height was reached by 31.1% of patients in the efficacy cohort, at an average age of 15.9 years for treatment-naïve and 15.7 years for pretreated patients.
Among the 35 treatment-naïve patients who achieved adult height, the average height SDS was –2.97 at baseline and –2.02 after treatment, which the researchers say is similar to the height SDS of –2.10 achieved by the 16 pretreated patients.
On average, the prepubertal treatment-naïve patients achieved a gain in peak-centred height velocity SDS over 3 years of +3.94, while a +0.47 gain was reported for prepubertal pretreated patients. The average height velocity at year 3 in the full efficacy cohort was 5.9 and 4.5 cm/year for treatment-naïve and pretreated patients, respectively, with corresponding values in prepubertal patients of 5.2 and 4.7 cm/year.
Analysis by karyotype revealed that treatment-naïve patients with classical 45,X TS had the most severe short stature at baseline and experienced the greatest improvement, with a height SDS of +1.32, the researchers note.
“Substantial height gains were observed in prepubertal individuals over 3 years of treatment, despite the use of doses at the lower end of those recommended”, summarise Zouater et al.
They comment: “This study also indicates that rhGH treatment and estradiol supplementation can be further improved to help individuals with TS to attain [adult height] closer to the population mean.”
During the study, 29.6% of treatment-naïve and 64.1% of pretreated patients began concomitant oestrogen therapy with oestradiol, oestradiol valerate, ethinyl oestradiol, conjugated oestrogen or another oestrogen formulation. One patient, who had previously received rhGH for 6 years before entering the study at age 11 years, began oxandrolone therapy.
Safety analysis showed that by data cutoff in August 2019, 49.4% of patients had discontinued rhGH therapy, most commonly after reaching adult height or bone age maturation (30.2%), reaching near adult height (16.3%) or a nonspecified reason (12.7%). Just 5.8% of patients permanently discontinued treatment because of an adverse event (AE).
Almost half (48.9%) of the 348 TS patients experienced an AE of any grade and 7.2% had a suspected drug-related AE, most frequently headache (n=4), impaired glucose intolerance (n=4), insulin-like growth factor elevation (n=2), injection site haematoma (n=2) or weight increase (n=2).
Most of the AEs were mild (39.9%) or moderate (24.4%) but 4.0% were severe and there was one (0.3%) possibly drug-related serious AE, namely intracranial hypertension, in an 11-year-old patient taking a rhGH dose of 48.0 µg/kg per day.
Of note, just 0.3% of patients had treatment-related scoliosis and there were no treatment-related cases of pancreatitis, the researchers say.
While there were “[n]o unexpected or concerning safety signals” in the PATRO Children study, the researchers conclude that “several well-known AEs were observed, confirming the need for ongoing patient monitoring.”
By Lynda Williams
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