TY - JOUR
T1 - Peak functional ability and age at loss of ambulation in Duchenne muscular dystrophy
AU - The UK Northstar Clinical Network
AU - Zambon, Alberto A.
AU - Ayyar Gupta, Vandana
AU - Ridout, Deborah
AU - Manzur, Adnan Y
AU - Baranello, Giovanni
AU - Trucco, Federica
AU - Muntoni, Francesco
AU - Tirupath, Sandya
AU - Douglas, Melanie
AU - McFetridge, Jaci
AU - Parasuraman, Deepak
AU - Alhaswani, Zoya
AU - McMurchie, Heather
AU - Rabb, Rosanna
AU - Majumdar, Anirban
AU - Vijayakumar, Kayal
AU - Amin, Sam
AU - Mason, Faye
AU - Frimpong-Ansah, Claire
AU - Gibbon, Frances
AU - Parson, Bethan
AU - Naismith, Karen
AU - Burslem, Julie
AU - Baxter, Alex
AU - Eadie, Clare
AU - Horrocks, Iain
AU - Di Marco, Marina
AU - Childs, Anne Marie
AU - Pallant, Lindsey
AU - Spinty, Stefan
AU - Shillington, Alison
AU - Gregson, Sarah
AU - Cheshman, Laura
AU - Wraige, Elizabeth
AU - Gowda, Vasantha
AU - Jungbluth, Heinz
AU - Sheehan, Jennie
AU - Hughes, Imelda
AU - Warner, Sinead
AU - Straub, Volker
AU - Guglieri, Michela
AU - Mayhew, Anna
AU - Chow, Gabby
AU - Williamson, Sarah
AU - Willis, Tracey
AU - Kulshrestha, Richa
AU - Emery, Nicholas
AU - Ramdas, Sithara
AU - Ramjattan, Hayley
AU - Ward, Catherine
N1 - Funding Information:
The support of the Muscular Dystrophy UK to the NorthStar Network, and of the MRC Neuromuscular Translational Research grant, is gratefully acknowledged. FM reports grants from Sarepta, grants from Wave, grants from PTC, personal fees from Roche, personal fees from Pfizer, from Sarepta and Dyne Therapeutics, outside the submitted work. Special thanks and appreciation go to the neuromuscular team at the Dubowitz Neuromuscular Centre, in particular to Anna Sarkozy, Pinki Munot, Stephanie Robb, Ros Quinlivan, Mariacristina Scoto, Mary Chesshyre, and the Great Ormond Street Hospital physiotherapy team for their role in assessing motor function in patients with DMD. A special acknowledgement goes to colleagues contributing to the NorthStar Network data set. We acknowledge the contribution and the support of Muscular Dystrophy UK to the Neuromuscular Centre at UCL. Lastly, we thank Stefano Previtali for review. The authors have stated that they had no interests that might be perceived as posing a conflict or bias.
Publisher Copyright:
© 2022 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.
PY - 2022/2/4
Y1 - 2022/2/4
N2 - Aim: To correlate the North Star Ambulatory Assessment (NSAA) and timed rise from floor (TRF) recorded at age of expected peak with age at loss of ambulation (LOA) in Duchenne muscular dystrophy (DMD). Method: Male children with DMD enrolled in the UK North Start Network database were included according to the following criteria: follow-up longer than 3 years, one NSAA record between 6 years and 7 years 6 months (baseline), at least one visit when older than 8 years. Data about corticosteroid treatment, LOA, genotype, NSAA, and TRF were analysed. Age at LOA among the different groups based on NSAA and TRF was determined by log-rank tests. Cox proportional hazard models were used for multivariable analysis. Results: A total of 293 patients from 13 different centres were included. Mean (SD) age at first and last visit was 5 years 6 months (1 year 2 months) and 12 years 8 months (2 years 11 months) (median follow-up 7 years 4 months). Higher NSAA and lower TRF at baseline were associated with older age at LOA (p<0.001). Patients scoring NSAA 32 to 34 had a probability of 0.61 of being ambulant when older than 13 years compared with 0.34 for those scoring 26 to 31. In multivariable analysis, NSAA, TRF, and corticosteroid daily regimen (vs intermittent) were all independently associated with outcome (p=0.01). Interpretation: Higher functional abilities at peak are associated with older age at LOA in DMD. This information is important for counselling families. These baseline measures should also be considered when designing clinical trials.
AB - Aim: To correlate the North Star Ambulatory Assessment (NSAA) and timed rise from floor (TRF) recorded at age of expected peak with age at loss of ambulation (LOA) in Duchenne muscular dystrophy (DMD). Method: Male children with DMD enrolled in the UK North Start Network database were included according to the following criteria: follow-up longer than 3 years, one NSAA record between 6 years and 7 years 6 months (baseline), at least one visit when older than 8 years. Data about corticosteroid treatment, LOA, genotype, NSAA, and TRF were analysed. Age at LOA among the different groups based on NSAA and TRF was determined by log-rank tests. Cox proportional hazard models were used for multivariable analysis. Results: A total of 293 patients from 13 different centres were included. Mean (SD) age at first and last visit was 5 years 6 months (1 year 2 months) and 12 years 8 months (2 years 11 months) (median follow-up 7 years 4 months). Higher NSAA and lower TRF at baseline were associated with older age at LOA (p<0.001). Patients scoring NSAA 32 to 34 had a probability of 0.61 of being ambulant when older than 13 years compared with 0.34 for those scoring 26 to 31. In multivariable analysis, NSAA, TRF, and corticosteroid daily regimen (vs intermittent) were all independently associated with outcome (p=0.01). Interpretation: Higher functional abilities at peak are associated with older age at LOA in DMD. This information is important for counselling families. These baseline measures should also be considered when designing clinical trials.
UR - http://www.scopus.com/inward/record.url?scp=85130841295&partnerID=8YFLogxK
U2 - 10.1111/dmcn.15176
DO - 10.1111/dmcn.15176
M3 - Article
C2 - 35385138
AN - SCOPUS:85130841295
SN - 0012-1622
VL - 64
SP - 979
EP - 988
JO - Developmental Medicine and Child Neurology
JF - Developmental Medicine and Child Neurology
IS - 8
ER -