{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:35:53Z","timestamp":1789785353406,"version":"4.0.1"},"reference-count":33,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk A\/S","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,19]]},"abstract":"Abstract<\/jats:title>\n \n Context<\/jats:title>\n The pretreatment blood transcriptome predicts growth response to daily growth hormone (GH) therapy with high accuracy.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n Investigate response prediction using pretreatment transcriptome in children with GH deficiency (GHD) treated with once-weekly somapacitan, a novel long-acting GH.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n REAL4 is a randomized, multinational, open-label, active-controlled parallel group phase 3 trial, comprising a 52-week main phase and an ongoing 3-year safety extension (NCT03811535). A total of 128\/200 treatment-na\u00efve prepubertal children with GHD consented to baseline blood transcriptome profiling. They were randomized 2:1 to subcutaneous somapacitan (0.16\u2005mg\/kg\/week) or daily GH (0.034\u2005mg\/kg\/day). Differential RNA-seq analysis and machine learning were used to predict therapy response.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n 121\/128 samples passed quality control. Children treated with somapacitan (n = 76) or daily GH (n = 45) were categorized based on fastest and slowest growing quartiles at week 52. Prediction of height velocity (HV; cm\/year) was excellent for both treatments (out of bag [OOB] area under curve [AUC]: 0.98-0.99; validation AUC: 0.83-0.84), as was prediction of secondary markers of growth response: HV standard deviation score (SDS) (0.99-1.0; 0.75-0.78), change from baseline height SDS (\u0394HSDS) (0.98-1.0; 0.61-0.75), and change from baseline insulin-like growth factor-I SDS (\u0394IGF-I SDS) (0.96-1.0; 0.85-0.88). Genes previously identified as predictive of GH therapy response were consistently better at predicting the fastest growers in both treatments in this study (OOB AUC: 0.93-0.97) than the slowest (0.67-0.85).<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Pretreatment transcriptome predicts first-year growth response in somapacitan-treated children with GHD. A common set of genes can predict the treatment response to both once-weekly somapacitan and conventional daily GH. This approach could potentially be developed into a clinically applicable pretreatment test to improve clinical management.<\/jats:p>\n <\/jats:sec>","DOI":"10.1210\/clinem\/dgad717","type":"journal-article","created":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T04:15:51Z","timestamp":1702095351000},"page":"1214-1221","source":"Crossref","is-referenced-by-count":9,"title":["Gene Expression Signatures Predict First-Year Response to Somapacitan Treatment in Children With Growth Hormone Deficiency"],"prefix":"10.1210","volume":"109","author":[{"given":"Terence","family":"Garner","sequence":"first","affiliation":[{"name":"Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester and Manchester Academic Health Science Centre , Manchester, M13 9WL , 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