{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:15:39Z","timestamp":1791976539084,"version":"4.4.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T00:00:00Z","timestamp":1646956800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T00:00:00Z","timestamp":1646956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Sandoz\/Hexal AG"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There are known geographical differences in growth hormone deficiency (GHD) patient populations and treatment practices. Here, we present a comparison of safety and effectiveness data from patients treated with recombinant human growth hormone (rhGH) in the USA versus other countries. PAtients TReated with Omnitrope\u00ae (PATRO) Children is an international, non-interventional study with Omnitrope\u00ae (somatropin, Sandoz Inc.). All visits and assessments are carried out according to routine clinical practice, and doses of Omnitrope\u00ae are given according to country-specific prescribing information. By September 2018, 294 patients had been enrolled in the USA (53% rhGH-na\u00efve) and 6206 patients had been enrolled across 13 other countries (international group; 86% rhGH-na\u00efve). The most common indication in both groups was GHD. Overall, 194 US patients (66%) and 2977 international patients (48%) experienced adverse events (AEs; 886 and 11,716 events, respectively), most of which were of mild or moderate intensity. The AEs were suspected to be treatment-related in five US patients (1.7%) and 452 international patients (7.3%). All reported neoplasms were benign, non-serious, and considered unrelated to rhGH therapy. No cases of diabetes mellitus or hyperglycemia were reported. In rhGH-na\u00efve GHD patients, after 3\u00a0years of rhGH therapy, the improvement in mean height SD score from baseline was\u2009+\u20091.25 and\u2009+\u20091.35 in US and international patients, respectively.<\/jats:p><jats:p><jats:italic>Conclusion<\/jats:italic>: Omnitrope\u00ae treatment appears to be well tolerated and effective in US patients and those from other countries. Across the pediatric indications included, there was no evidence of an increased risk of developing uncommon or unexpected AEs with rhGH.<\/jats:p><jats:p><jats:italic>Trial registration<\/jats:italic>: NA.<jats:table-wrap><jats:table><jats:tbody>\n                    <jats:tr>\n                      <jats:td colspan=\"2\"><jats:bold>What is Known:<\/jats:bold><jats:italic>\u2022 Continued monitoring of patients treated with recombinant human growth hormone (rhGH) is important, particularly in terms of diabetogenic potential and the risk of malignancies.<\/jats:italic><jats:italic>\u2022 The PAtients TReated with Omnitrope\u00ae (PATRO) Children study is a long-term, post-marketing surveillance program for the rhGH Omnitrope\u00ae<\/jats:italic>.<\/jats:td>\n                    <\/jats:tr>\n                    <jats:tr>\n                      <jats:td colspan=\"2\"><jats:bold>What is New:<\/jats:bold><jats:italic>\u2022 Omnitrope\u00ae is well tolerated and effective in US patients, and those from other countries.<\/jats:italic><jats:italic>\u2022 Across all indications included, there were no unexpected adverse events and there was no evidence of an increased risk of developing malignancies or diabetes.<\/jats:italic><\/jats:td>\n                    <\/jats:tr>\n                  <\/jats:tbody><\/jats:table><\/jats:table-wrap><\/jats:p>","DOI":"10.1007\/s00431-022-04409-8","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T07:03:01Z","timestamp":1646982181000},"page":"2367-2378","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Safety and effectiveness of Omnitrope\u00ae (somatropin) in PATRO Children: a multi-center, post-marketing surveillance study comparison of US and international cohort data"],"prefix":"10.1007","volume":"181","author":[{"given":"Philippe","family":"Backeljauw","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankar","family":"Kanumakala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Loche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl Otfried","family":"Schwab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley S.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"McCormick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hichem","family":"Zouater","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Zabransky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,11]]},"reference":[{"key":"4409_CR1","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.2147\/DDDT.S130317","volume":"11","author":"P Saenger","year":"2017","unstructured":"Saenger P (2017) Ten years of biosimilar recombinant human growth hormone in Europe. Drug Des Devel Ther 11:1505\u20131507","journal-title":"Drug Des Devel Ther"},{"key":"4409_CR2","unstructured":"European Medicines Agency (EMA) (2018) Omnitrope Summary of Product Characteristics (SmPC). https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/omnitrope-epar-product-information_en.pdf. Accessed 1 Jun 2021"},{"key":"4409_CR3","unstructured":"US Food and Drug Administration (2017) Omnitrope Highlights of Prescribing Information. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/021426s022lbl.pdf. Accessed 1 Dec 2020"},{"key":"4409_CR4","unstructured":"European Medicines Agency (EMA) (2018) Omnitrope European Public Assessment Report (EPAR). https:\/\/www.ema.europa.eu\/en\/documents\/overview\/omnitrope-epar-summary-public_en.pdf. Accessed 1 Jun\u00a02021"},{"key":"4409_CR5","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.biologicals.2011.06.003","volume":"39","author":"AV Klein","year":"2011","unstructured":"Klein AV (2011) The first subsequent entry biologic authorized for market in Canada: the story of Omnitrope, a recombinant human growth hormone. Biologicals 39:278\u2013281","journal-title":"Biologicals"},{"key":"4409_CR6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1177\/2042018813479644","volume":"4","author":"R Pfaffle","year":"2013","unstructured":"Pfaffle R, Schwab KO, Marginean O, Walczak M, Szalecki M, Schuck E, Zabransky M, Zucchini S (2013) Design of, and first data from, PATRO Children, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope\u00ae in children requiring growth hormone treatment. Ther Adv Endocrinol Metab 4:3\u201311","journal-title":"Ther Adv Endocrinol Metab"},{"key":"4409_CR7","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1515\/jpem-2020-0360","volume":"34","author":"P Backeljauw","year":"2021","unstructured":"Backeljauw P, Miller BS, Levy R, McCormick K, Zouater H, Zabransky M, Campbell K (2021) PATRO Children, a multi-center, non-interventional study of the safety and effectiveness of Omnitrope(\u00ae) (somatropin) treatment in children: update on the United States cohort. J Pediatr Endocrinol Metab 34:431\u2013440","journal-title":"J Pediatr Endocrinol Metab"},{"key":"4409_CR8","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nrendo.2018.22","volume":"14","author":"MB Ranke","year":"2018","unstructured":"Ranke MB, Wit JM (2018) Growth hormone - past, present and future. 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Eur J Endocrinol 174:1\u20139","journal-title":"Eur J Endocrinol"},{"key":"4409_CR11","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12902-019-0464-2","volume":"19","author":"P Beck-Peccoz","year":"2019","unstructured":"Beck-Peccoz P, H\u00f6ybye C, Murray RD, Simsek S, Zabransky M, Zouater H, Stalla G (2019) No increased risk of glucose metabolism disorders in adults with growth hormone deficiency undergoing long-term treatment with biosimilar somatropin (Omnitrope\u00ae): data from an observational, longitudinal study. BMC Endocr Disord 19:138","journal-title":"BMC Endocr Disord"},{"key":"4409_CR12","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1210\/jc.2009-0178","volume":"95","author":"J Bell","year":"2010","unstructured":"Bell J, Parker KL, Swinford RD, Hoffman AR, Maneatis T, Lippe B (2010) Long-term safety of recombinant human growth hormone in children. 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Am J Pharm Benefits 6:e9\u201317","journal-title":"Am J Pharm Benefits"}],"container-title":["European Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-022-04409-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00431-022-04409-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-022-04409-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T12:13:53Z","timestamp":1652703233000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00431-022-04409-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,11]]},"references-count":25,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["4409"],"URL":"https:\/\/doi.org\/10.1007\/s00431-022-04409-8","relation":{},"ISSN":["1432-1076"],"issn-type":[{"value":"1432-1076","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,11]]},"assertion":[{"value":"13 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The PATRO Children study protocol was approved by the ethics review committee of all participating centers in accordance with national laws and regulations. All procedures performed were in accordance with the ethical standards of these committees and with the 1964 Declaration of Helsinki and its later amendments.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All patients (and\/or their parents\/guardians where the patient was a minor) have given their written informed consent to participate in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Philippe Backeljauw, Shankar Kanumakala, Sandro Loche, and Karl Otfried Schwab are members of the PATRO Children study Global Steering Committee. Bradley S Miller, Richard Levy, and Kenneth McCormick are investigators in the PATRO Children study. Hichem Zouater, Markus Zabransky, and Kim Campbell are employees of Sandoz.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}