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. 2024 Dec;31(12):e16415.
doi: 10.1111/ene.16415. Epub 2024 Sep 9.

Relationship between growth and ambulation loss in Duchenne muscular dystrophy boys on steroids

Georgia Stimpson  1 , Deborah Ridout  2 , Anna Sarkozy  1   3 , Adnan Manzur  1   3 , Francesco Muntoni  1   3 , Giovanni Baranello  1   3 ; NorthStar Network
Affiliations

Relationship between growth and ambulation loss in Duchenne muscular dystrophy boys on steroids

Georgia Stimpson et al. Eur J Neurol. 2024 Dec.

Abstract

Background and purpose: Treatment with glucocorticoids (GCs) is part of the standard of care in Duchenne muscular dystrophy, but excess weight gain and height stunting are common side-effects. It is still unclear how these growth-related side-effects affect motor function.

Methods: This retrospective cohort study utilized 2228 observations from 648 participants in the UK NorthStar database who had growth and ambulation data recorded between 2006 and 2020. Joint modelling was used to analyse the effect of longitudinal growth centiles on loss of ambulation with respect to GC type and regimen.

Results: Loss of ambulation was observed in 113 patients. National estimates of loss of ambulation age were updated by GC group and showed no significant association between loss of ambulation risk and absolute growth centile. However, yearly drift in weight and/or height centile had an associated risk effect on loss of ambulation. Over a 2-year period, a yearly drift in weight from the 50th to the 75th, 75th to the 90th and 90th to the 95th centile was associated with 138%, 118% and 64% increased risk of loss of ambulation, respectively. Conversely, a 2-year drift in height from the 50th to the 25th, 25th to the 10th and 10th to the 5th centile was associated with 53%, 49% and 35% decreased risk of loss of ambulation, respectively.

Conclusions: Our results suggest a complex relationship between growth and loss of ambulation in Duchenne muscular dystrophy boys on chronic GCs, the first step in understanding the effects of drugs which also affect growth patterns.

Keywords: Duchenne muscular dystrophy; glucocorticoids; growth; walking.

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Conflict of interest statement

F.M. reports participation in Scientific Advisory boards and teaching initiatives for Novartis, Biogen, Roche; he is involved as an investigator in clinical trials from Novartis, Biogen and Roche. Both institutions (UCL and GOSH) receive funding from Biogen and Roche for the SMAREACH SMA registry. G.B. is PI of clinical trials 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. G.S., D.R., A.M. and A.S. have no conflict of interest to declare.

Figures

FIGURE 1
FIGURE 1
Data cleaning process.
FIGURE 2
FIGURE 2
Loss of ambulation by GC group.
FIGURE 3
FIGURE 3
Forest plot of variables which impact loss of ambulation (a), and mean weight trajectory for age by GC group (b). Here, the red line in subplot (a) represents the GC naïve group.
FIGURE 4
FIGURE 4
Forest plot of variables which impact loss of ambulation (a), and mean height trajectory for age by GC group (b). Here, the red line in subplot (a) represents the GC naïve group.
FIGURE 5
FIGURE 5
Forest plot of variables which impact loss of ambulation (a), and mean BMI trajectory for age by GC group (b). Here, the red line in subplot (a) represents the GC naïve group.
See this image and copyright information in PMC

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