[en] OBJECTIVES: The objective of this study is to analyse retrospective, observational, longitudinal growth (weight, height and BMI) data in ambulatory boys aged 5-12 years with Duchenne muscular dystrophy (DMD).
BACKGROUND: We considered glucocorticoids (GC) use, dystrophin isoforms and amenability to exon 8, 44, 45, 51 and 53 skipping drug subgroups, and the impact of growth on loss of ambulation. We analysed 598 boys, with 2604 observations. This analysis considered patients from the UK NorthStar database (2003-2020) on one of five regimes: "GC naïve", "deflazacort daily" (DD), "deflazacort intermittent" (DI), "prednisolone daily" (PD) and "prednisolone intermittent" (PI). A random slope model was used to model the weight, height and BMI SD scores (using the UK90).
RESULTS: The daily regime subgroups had significant yearly height stunting compared to the GC naïve subgroup. Notably, the average height change for the DD subgroup was 0.25 SD (95% CI - 0.30, - 0.21) less than reference values. Those with affected expression of Dp427, Dp140 and Dp71 isoforms were 0.77 (95% CI 0.3, 1.24) and 0.82 (95% CI 1.28, 0.36) SD shorter than those with Dp427 and/or Dp140 expression affected respectively. Increased weight was not associated with earlier loss of ambulation, but taller boys still ambulant between the age of 10 and 11 years were more at risk of losing ambulation.
CONCLUSION: These findings may provide further guidance to clinicians when counselling and discussing GCs commencement with patients and their carers and may represent a benchmark set of data to evaluate the effects of new generations of GC.
Disciplines :
Neurology Pediatrics
Author, co-author :
Stimpson, Georgia; Developmental Neuroscience Research and Teaching Department, Faculty of Population Health Sciences, Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK
Raquq, Sarah; Developmental Neuroscience Research and Teaching Department, Faculty of Population Health Sciences, Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK
Chesshyre, Mary; Developmental Neuroscience Research and Teaching Department, Faculty of Population Health Sciences, Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK ; NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Hospital NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
Fewtrell, Mary; Population, Policy and Practice Department, Faculty of Population Health Sciences, UCL Great Ormond Street Institute of Child Health, London, UK
Ridout, Deborah; Population, Policy and Practice Department, Faculty of Population Health Sciences, UCL Great Ormond Street Institute of Child Health, London, UK
Sarkozy, Anna; Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK ; NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Hospital NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
Manzur, Adnan; Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK ; NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Hospital NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
Ayyar Gupta, Vandana; Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK
De Amicis, Ramona; International Centre for the Assessment of Nutritional Status (ICANS), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
Muntoni, Francesco; Developmental Neuroscience Research and Teaching Department, Faculty of Population Health Sciences, Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK ; NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Hospital NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
Baranello, Giovanni ; Developmental Neuroscience Research and Teaching Department, Faculty of Population Health Sciences, Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK. g.baranello@ucl.ac.uk ; NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Hospital NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK. g.baranello@ucl.ac.uk
NorthStar Network
Servais, Laurent ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pédiatrie ; University of Oxford > MDUK Oxford Neuromuscular Centre
GS, SR, MC, MF, DR, VAG, RDA, AS and AM have no conflict of interest. FM is supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre and has received speaker and consultancy honoraria from Sarepta Therapeutics, Avexis, PTC Therapeutics, Roche and Pfizer. The views expressed in this paper are his and not necessarily those of the NHS, NIHR or the department of health. GB is PI of clinical trials Sponsored by Pfizer, NS Pharma, and Reveragen, and has received speaker and/or consulting fees from Sarepta, PTC Therapeutics, Biogen, Novartis Gene Therapies, Inc. (AveXis), and Roche and has worked as principal investigator of SMA studies sponsored by Novartis Gene Therapies, Inc., and Roche.The Northstar project is funded by MDUK (Muscular Dystrophy UK) under a 5 year grant and the funding initially started from 01/11/2016 and is due to end on 30/06/2022. The current grant number is: Grant Reference 16NMDB-DB60-0004–5.We are grateful to the DMD patients and their families, the North Star clinical network senior clinico-academic coordinator Dr Vandana Ayyar Gupta and the Northstar network leads, Professor Francesco Muntoni (f.muntoni@ucl.ac.uk), Dr Adnan Manzur (adnan.manzur@gosh.nhs.uk) and Dr Giovanni Baranello (g.baranello@ucl.ac.uk). We are grateful to Muscular Dystrophy UK (MDUK) for funding the North Star network and Certus Technology Associates Limited for hosting the database. The North Star DMD Network is support by a Grant from Muscular Dystrophy UK to Dr Adnan Manzur and Prof Francesco Muntoni, at UCL. Dr. Baranello, Georgia Stimpson and Sarah Raquq are supported by a Grant from the Great Ormond Street Hospital Children's Charity and Muscular Dystrophy UK. The NorthStar Network contributors are: Gautam Ambegaonkar, Zoya Alhaswani, Alex Baxter, Anne-Marie Childs, Gabby Chow, Christian de Goede, Miguel Fernandez, Frances Gibbon, Vasantha Gowda, Michela Guglieri, Tony Hart, Gemunu Hewawitharana, Iain Horrocks, Imelda Hughes, Marjorie Illingworth, Deepa Krishnakumar, Anirban Majumdar, Chiara Marini-Bettolo, Min Ong, Deepak Parasuraman, Sithara Ramdas, Laurent Servais, Kate Skone, Stefan Spinty, Elma Stephens, Volker Straub, Sandya Tirupathi, Neil Thomas, Tracey Willis, Cathy White, Jarod Wong, Elizabeth Wraige, Kayal Vijayakumar, Karen Naismith.We are grateful to the DMD patients and their families, the North Star clinical network senior clinico-academic coordinator Dr Vandana Ayyar Gupta and the Northstar network leads, Professor Francesco Muntoni (f.muntoni@ucl.ac.uk), Dr Adnan Manzur (adnan.manzur@gosh.nhs.uk) and Dr Giovanni Baranello (g.baranello@ucl.ac.uk). We are grateful to Muscular Dystrophy UK (MDUK) for funding the North Star network and Certus Technology Associates Limited for hosting the database. The North Star DMD Network is support by a Grant from Muscular Dystrophy UK to Dr Adnan Manzur and Prof Francesco Muntoni, at UCL. Dr. Baranello, Georgia Stimpson and Sarah Raquq are supported by a Grant from the Great Ormond Street Hospital Children's Charity and Muscular Dystrophy UK.
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