{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:35:57Z","timestamp":1789785357020,"version":"4.0.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Long-acting recombinant human growth hormone (rhGH) has transformed growth hormone deficiency (GHD) treatment. However, the possibility and rationality for flexible time regimen are pending.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We studied the efficacy of biweekly <jats:italic>versus<\/jats:italic> weekly PEGylated rhGH (PEG-rhGH) therapy in GHD children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Patients<\/jats:title><jats:p>This multicenter, phase IV trial with a non-inferiority threshold \u226520% enrolled 585 Tanner stage I GHD children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Intervention<\/jats:title><jats:p>Subjects randomly received 0.20 mg\/kg once-weekly or biweekly PEG-rhGH, or 0.25 mg\/kg.w rhGH once daily for 26 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measure<\/jats:title><jats:p>The primary outcome was height SD scores for chronological age (HtSDS<jats:sub>CA<\/jats:sub>) at week 26 and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At week 26, the median HtSDS<jats:sub>CA<\/jats:sub> changed from \u22122.75, \u22122.82, and \u22122.78 to \u22122.31, \u22122.43, and \u22122.28 with weekly and biweekly PEG-rhGH, and daily rhGH, respectively. The difference in HtSDS<jats:sub>CA<\/jats:sub> was 0.17 \u00b1 0.28 between weekly and biweekly PEG-rhGH, and 0.17 \u00b1 0.27 between daily rhGH and biweekly PEG-rhGH, failing the non-inferiority threshold. Nevertheless, the height velocity of children receiving biweekly PEG-rhGH reached 76.42%\u201390.34% and 76.08%\u201390.60% that of children receiving weekly PEG-rhGH and daily rhGH, respectively. The rate of AEs was comparable among the groups. No statistical difference was observed in IGF-2 and IGFBP-2 levels among the groups. IGFBP-2 levels decreased over time in all groups, with no notable difference in IGF-2 and IGFBP-2 changes among the three treatment groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although notably promoted height velocity, biweekly PEG-rhGH failed the non-inferiority threshold as compared with either weekly PEG-rhGH or daily rhGH. Compared with short-term rhGH, long-acting PEG-rhGH did not significantly increase tumor-associated IGF-2 and IGFBP-2 expressions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p><jats:uri>clinicaltrials.gov<\/jats:uri>, identifier NCT02976675.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.779365","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:32:40Z","timestamp":1638315160000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted 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