دورية أكاديمية
Gene Expression Signatures Predict First-Year Response to Somapacitan Treatment in Children With Growth Hormone Deficiency.
| العنوان: | Gene Expression Signatures Predict First-Year Response to Somapacitan Treatment in Children With Growth Hormone Deficiency. |
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| المؤلفون: | Garner T; Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester and Manchester Academic Health Science Centre, Manchester, M13 9WL, UK., Clayton P; Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester and Manchester Academic Health Science Centre, Manchester, M13 9WL, UK.; Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, M13 9WL, UK., Højby M; Novo Nordisk, Clinical Drug Development, 2860 Søborg, Denmark., Murray P; Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester and Manchester Academic Health Science Centre, Manchester, M13 9WL, UK.; Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, M13 9WL, UK., Stevens A; Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester and Manchester Academic Health Science Centre, Manchester, M13 9WL, UK. |
| المصدر: | The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Apr 19; Vol. 109 (5), pp. 1214-1221. |
| نوع المنشور: | Randomized Controlled Trial; Clinical Trial, Phase III; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : New York : Oxford University Press Original Publication: Springfield, Ill. : Charles C. Thomas |
| مواضيع طبية MeSH: | Dwarfism, Pituitary*/drug therapy , Dwarfism, Pituitary*/genetics , Histidine* , Human Growth Hormone* , Mannitol* , Phenol*, Child ; Humans ; Body Height ; Growth Hormone/deficiency ; Growth Hormone/therapeutic use ; Insulin-Like Growth Factor I/metabolism ; Transcriptome |
| مستخلص: | Context: The pretreatment blood transcriptome predicts growth response to daily growth hormone (GH) therapy with high accuracy. Objective: Investigate response prediction using pretreatment transcriptome in children with GH deficiency (GHD) treated with once-weekly somapacitan, a novel long-acting GH. Methods: 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-naïve prepubertal children with GHD consented to baseline blood transcriptome profiling. They were randomized 2:1 to subcutaneous somapacitan (0.16 mg/kg/week) or daily GH (0.034 mg/kg/day). Differential RNA-seq analysis and machine learning were used to predict therapy response. Results: 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 (ΔHSDS) (0.98-1.0; 0.61-0.75), and change from baseline insulin-like growth factor-I SDS (ΔIGF-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). Conclusion: 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. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.) |
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| معلومات مُعتمدة: | Novo Nordisk A/S |
| فهرسة مساهمة: | Keywords: and RNA sequencing; growth hormone deficiency; long-acting growth hormone; predictive markers; pretreatment blood transcriptome; somapacitan |
| المشرفين على المادة: | 9002-72-6 (Growth Hormone) 4QD397987E (Histidine) 12629-01-5 (Human Growth Hormone) 67763-96-6 (Insulin-Like Growth Factor I) 3OWL53L36A (Mannitol) 339NCG44TV (Phenol) 0 (somapacitan) |
| تواريخ الأحداث: | Date Created: 20231209 Date Completed: 20240422 Latest Revision: 20240430 |
| رمز التحديث: | 20240501 |
| مُعرف محوري في PubMed: | PMC11031233 |
| DOI: | 10.1210/clinem/dgad717 |
| PMID: | 38066644 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-7197 |
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| DOI: | 10.1210/clinem/dgad717 |