دورية أكاديمية
Gene expression signatures predict first-year response to somapacitan treatment in children with GH deficiency
| العنوان: | Gene expression signatures predict first-year response to somapacitan treatment in children with GH deficiency |
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| المؤلفون: | Garner, Terence, Clayton, Peter, Højby, Michael, Murray, Philip, Stevens, Adam |
| المصدر: | Garner , T , Clayton , P , Højby , M , Murray , P & Stevens , A 2023 , ' Gene expression signatures predict first-year response to somapacitan treatment in children with GH deficiency ' , The Journal of Clinical Endocrinology & Metabolism . https://doi.org/10.1210/clinem/dgad717Test |
| سنة النشر: | 2023 |
| المجموعة: | The University of Manchester: Research Explorer - Publications |
| مصطلحات موضوعية: | Predictive Markers, Growth Hormone Deficiency, Long-acting Growth Hormone, Somapacitan, Pre-treatment Blood Transcriptome, RNA Sequencing |
| الوصف: | Context: The pre-treatment blood transcriptome predicts growth response to daily GH therapy with high accuracy. Objective: Investigate response prediction using pre-treatment transcriptome in children with GH deficiency (GHD) treated with once-weekly somapacitan, a novel long-acting GH. Design: REAL4 is a randomised, multinational, open-labelled, active-controlled parallel group phase 3 trial, comprising a 52-week main phase and an ongoing 3-year safety extension (NCT03811535). Patients: 128/200 treatment-naïve prepubertal children with GHD consented to baseline blood transcriptome profiling. Interventions: Randomized 2:1 to subcutaneous somapacitan (0.16 mg/kg/week) or daily GH (0.034 mg/kg/day). Methods and main outcome measures: Differential RNA-seq analysis and machine learning to predict therapy response. Results: 121/128 samples passed quality control. Children treated with somapacitan (n=76) or daily GH (n=45) were categorised based on fastest and slowest growing quartiles at week 52. Prediction of height velocity (HV; cm/year) was excellent for both treatments (OOB AUC: 0.98–0.99; validation AUC: 0.83-0.84), as was prediction of secondary markers of growth response: HV SD 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). Conclusions: Pre-treatment 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 pre-treatment test to improve clinical management. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://research.manchester.ac.uk/en/publications/b9ef4da4-6cba-40c5-9694-cd8b63673368Test |
| DOI: | 10.1210/clinem/dgad717 |
| DOI: | 10.1210/clinem/dgad717/7462793 |
| الإتاحة: | https://doi.org/10.1210/clinem/dgad717Test https://research.manchester.ac.uk/en/publications/b9ef4da4-6cba-40c5-9694-cd8b63673368Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.3B6D6F2B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1210/clinem/dgad717 |
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