https://orcid.org/0000-0003-4558-8533
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Abstract
Purpose
Omnitrope® (somatropin) was approved as a biosimilar recombinant human growth hormone (rhGH) in 2006. Here, we report final data from the PAtients TReated with Omnitrope® (PATRO) Children study, a post-marketing surveillance study designed to monitor the long-term safety and effectiveness of this treatment in pediatric patients.
Methods
The study population included all pediatric patients treated with Omnitrope® (biosimilar rhGH), administered via daily injection, in routine clinical practice. The primary objective was to assess long-term safety, with effectiveness assessed as a secondary objective.
Results
In total, 7359 patients were enrolled and treated in the PATRO Children study; 86.0% were treatment-naïve at baseline. Growth hormone deficiency was the most frequent indication (57.9%), followed by patients born small for gestational age (SGA; 26.6%). The mean (SD) duration of exposure to biosimilar rhGH was 3.66 years (2.39). A total of 16,628 adverse events (AEs) were reported in 3981 (54.1%) patients, most of which were mild/moderate. AEs suspected to be treatment related occurred in 8.3% of patients, most frequently headache (1.6%), injection-site pain (1.1%), or injection-site hematoma (1.1%). The incidence rate (IR) of type 2 diabetes mellitus was 0.11 per 1000 person-years (PY) across all patients, and 0.13 per 1000 PY in patients born SGA. The IR of newly diagnosed primary malignancies was 0.22 per 1000 PY across all patients. In the 6589 patients included in the effectiveness population, a sustained catch-up growth was observed across all indications. After 5 years of treatment, height SDS increased from baseline by a median (range) of +1.79 (–3.7 to 6.2) in treatment-naïve patients and +0.73 (–1.4 to 3.7) in pretreated patients.
Conclusion
This final analysis of the PATRO Children study indicates that biosimilar rhGH is well tolerated and effective in real-world clinical practice. These data are consistent with the well-characterized safety profile of rhGH treatment in pediatric patients.
Plain Language Summary
Why was the study done?
Injections of growth hormone medicine can be used to increase height velocity in children with growth disorders.
It is important to monitor the safety of long-term growth hormone treatment, especially regarding the risk of cancer and diabetes.
What did the researchers do?
PATRO Children was a study designed to look at the safety of using a growth hormone medicine for long periods of time.
This study included children with several different growth disorders who were treated with a growth hormone medicine called Omnitrope®, which is administered via daily injections, and followed them throughout their treatment.
The researchers aimed to evaluate the risk of specific safety concerns in these patients, including cancer and diabetes.
What did the researchers find?
A total of 7359 patients were enrolled from 304 sites around the world.
Overall, 8.3% of patients had an adverse reaction that was considered to be related to growth hormone treatment.
The most common adverse reaction considered related to growth hormone was headache, which occurred in 1.6% of patients.
The risk of developing diabetes and cancer was low and comparable to what has been seen in previous studies in patients treated with growth hormone, and in the general population.
What do the findings mean?
The adverse reactions seen in this study were consistent with the well-characterized safety profile of growth hormone treatment in pediatric patients. This supports previous studies showing growth hormone treatment is not associated with an increased risk of cancer or diabetes in children.
Abbreviations
AE, adverse event; BMI, body mass index; CNS, central nervous system; CRI, chronic renal insufficiency;eCRF, electronic case report form; EMA, European Medicines Agency; GeNeSIS, Genetics and Neuroendocrinology of Short Stature International Study; GHD, growth hormone deficiency; IGF-I, insulin-like growth factor I; iNCGS, International Cooperative Growth Study NutropinAq® European Registry; IR, incidence rate; ISS, idiopathic short stature; KIGS, Kabi/Pfizer International Growth Database; LCH, Langerhans cell histiocytosis; PATRO, PAtients TReated with Omnitrope®; PC, peak centered; PH–TH, projected height minus targeted height; PWS, Prader-Willi syndrome; PY, person-years; rhGH, recombinant human growth hormone; SAE, serious adverse event; SAF, safety analysis set; SAGhE, Safety and Appropriateness of Growth hormone treatments in Europe; SD, standard deviation; SDS, standard deviation score; SGA, small for gestational age; T1D, type 1 diabetes mellitus; T2D, type 2 diabetes mellitus; TS, Turner syndrome; UK, United Kingdom; USA, United States.
Ethics Approval and Informed Consent
The PATRO Children study protocol was approved by the ethics review committee of participating centers in accordance with national laws and regulations. The study was conducted according to the ethical principles of the Declaration of Helsinki (1964) and its later amendments. All patients (and/or their parents/guardians) provided written informed consent. Patients are permitted to withdraw their informed consent at any time or discontinue treatment for any reason.
Acknowledgments
The authors would like to thank all patients and investigators who participated in the PATRO Children study. Medical writing support was provided by Eve Blumson Ph.D. and Caroline McGown Ph.D. of Apollo, OPEN Health Communications, and funded by Sandoz/Hexal AG, in accordance with Good Publication Practice (GPP) guidelines (www.ismpp.org/gpp-2022). Statistical input was provided by Masiur Rahman of Novartis Pharmaceuticals, Wallingford, CT, USA.
Disclosure
Sandro Loche is a member of the PATRO Children Advisory Board and the PATRO Children Global Steering Committee, and has received advisory board and lecture fees from Sandoz, Merck Serono, Ipsen, and Pfizer. Shankar Kanumakala has received support to attend scientific meetings from Sandoz in previous years, and is a member of the PATRO Children Global Steering Committee. Philippe Backeljauw is a member of the PATRO Children Advisory Board, and has received advisory board, consultancy, and lecture fees from Novartis/Sandoz, BioMarin, Ascendis, Tolmar, Cavalry Biosciences, Novo Nordisk, and Ipsen. Karl Otfried Schwab is a member of the German PATRO Children Advisory Board and the PATRO Children Advisory Board, and has received advisory board and lecture fees from Akcea, Alexion, Merck Healthcare, Novartis, Pfizer, and Sanofi-Aventis. Alfonso M Lechuga-Sancho is a member of an external advisory board for Sandoz and Ipsen, and has received research grants from Abbott, Medtronic, Menarini, Merck Serono, Sanofi, and Novo Nordisk. Altaher Esmael and Markus Zabransky are employees of HEXAL AG (a Sandoz company). Dragan Urosevic is an employee of Novartis Sandoz Biopharmaceutical AG. Anca Boldea was an employee of HEXAL AG (a Sandoz company) when the study and manuscript development were undertaken. The authors report no other conflicts of interest in this work.