Growth pattern trajectories in boys with Duchenne muscular dystrophy
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Published:2022-01-24
Issue:1
Volume:17
Page:
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ISSN:1750-1172
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Container-title:Orphanet Journal of Rare Diseases
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language:en
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Short-container-title:Orphanet J Rare Dis
Author:
Stimpson Georgia, Raquq Sarah, Chesshyre Mary, Fewtrell Mary, Ridout Deborah, Sarkozy Anna, Manzur Adnan, Ayyar Gupta Vandana, De Amicis Ramona, Muntoni Francesco, Baranello GiovanniORCID, Ambegaonkar Gautam, Alhaswani Zoya, Baxter Alex, Childs Anne-Marie, Chow Gabby, De Goede Christian, Fernandez Miguel, Gibbon Frances, Gowda Vasantha, Guglieri Michela, Hart Tony, Hewawitharana Gemunu, Horrocks Iain, Hughes Imelda, Illingworth Marjorie, Krishnakumar Deepa, Majumdar Anirban, Marini-Bettolo Chiara, Ong Min, Parasuraman Deepak, Ramdas Sithara, Servais Laurent, Skone Kate, Spinty Stefan, Stephens Elma, Straub Volker, Tirupathi Sandya, Thomas Neil, Willis Tracey, White Cathy, Wong Jarod, Wraige Elizabeth, Vijayakumar Kayal, Naismith Karen,
Abstract
Abstract
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.
Funder
Muscular Dystrophy UK
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Genetics (clinical),General Medicine
Reference39 articles.
1. Blake DJ, Weir A, Newey SE, Davies KE. Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev. 2002;82:291–329. 2. Mendell JR, Rodino-Klapac LR, Sahenk Z, Roush K, Bird L, Lowes LP, et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013;74(5):637–47. 3. Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J, et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016;79(2):257–71. 4. Wagner KR, Kuntz NL, Koenig E, East L, Upadhyay S, Han B, et al. Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: a randomized, double-blind, placebo-controlled, dose-titration trial. Muscle Nerve. 2021;64(3):285–92. 5. Frank DE, Schnell FJ, Akana C, El-Husayni SH, Desjardins CA, Morgan J, et al. Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology. 2020;94(21):e2270–82.
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