TY - JOUR
T1 - Categorizing natural history trajectories of ambulatory function measured by the 6-minute walk distance in patients with Duchenne muscular dystrophy
AU - Mercuri, Eugenio Maria
AU - Signorovitch, James Edward
AU - Swallow, Elyse
AU - Song, Jinlin
AU - Ward, Susan J.
AU - Pane, Marika
AU - Mazzone, Elena Stacy
AU - Messina, S.
AU - Vita, G. L.
AU - Sormani, M. P.
AU - D'Amico, A.
AU - D'Amico, Adele
AU - Berardinelli, A.
AU - Magri, F.
AU - Comi, G. P.
AU - Baranello, G.
AU - Baranello, Giovanni
AU - Mongini, T.
AU - Pini, A.
AU - Battini, R.
AU - Battini, Roberta
AU - Pegoraro, E.
AU - Bruno, C.
AU - Politano, L.
AU - Previtali, S.
AU - Binks, M. H.
AU - Campion, G.
AU - Charnas, L.
AU - Kaye, E.
AU - Kelly, M.
AU - Morris, C.
AU - Reha, A.
PY - 2016
Y1 - 2016
N2 - High variability in patients' changes in 6 minute walk distance (6MWD) over time has complicated clinical trials of treatment efficacy in Duchenne muscular dystrophy (DMD). We assessed whether boys with DMD could be grouped into classes that shared similar ambulatory function trajectories as measured by 6MWD. Ambulatory boys aged 5 years or older with genetically confirmed DMD who were enrolled in a natural history study at 11 care centers throughout Italy were included. For each boy, standardized assessments of 6MWD were available at annual intervals spanning 3 years. Trajectories of 6MWD vs. age and trajectories of 6MWD vs. time from enrollment were examined using latent class analysis. A total of 96 boys were included. At enrollment, the mean age was 8.3 years (mean 6MWD: 374 meters). After accounting for age, baseline 6MWD, and steroid use, four latent trajectory classes were identified as explaining 3-year 6MWD outcomes significantly better than a single average trajectory. Patient trajectories of 6MWD change from enrollment were categorized as having fast decline (n = 25), moderate decline (n = 19), stable function (n = 37), and improving function (n = 15) during the 3-year follow-up. After accounting for trajectory classes, the standard deviation of variation in 6MWD was reduced by approximately 40%. The natural history of ambulatory function in DMD may be composed of distinct trajectory classes. The extent to which trajectories are associated with novel and established prognostic factors warrants further study. Reducing unexplained variation in patient outcomes could help to further improve DMD clinical trial design and analysis.
AB - High variability in patients' changes in 6 minute walk distance (6MWD) over time has complicated clinical trials of treatment efficacy in Duchenne muscular dystrophy (DMD). We assessed whether boys with DMD could be grouped into classes that shared similar ambulatory function trajectories as measured by 6MWD. Ambulatory boys aged 5 years or older with genetically confirmed DMD who were enrolled in a natural history study at 11 care centers throughout Italy were included. For each boy, standardized assessments of 6MWD were available at annual intervals spanning 3 years. Trajectories of 6MWD vs. age and trajectories of 6MWD vs. time from enrollment were examined using latent class analysis. A total of 96 boys were included. At enrollment, the mean age was 8.3 years (mean 6MWD: 374 meters). After accounting for age, baseline 6MWD, and steroid use, four latent trajectory classes were identified as explaining 3-year 6MWD outcomes significantly better than a single average trajectory. Patient trajectories of 6MWD change from enrollment were categorized as having fast decline (n = 25), moderate decline (n = 19), stable function (n = 37), and improving function (n = 15) during the 3-year follow-up. After accounting for trajectory classes, the standard deviation of variation in 6MWD was reduced by approximately 40%. The natural history of ambulatory function in DMD may be composed of distinct trajectory classes. The extent to which trajectories are associated with novel and established prognostic factors warrants further study. Reducing unexplained variation in patient outcomes could help to further improve DMD clinical trial design and analysis.
KW - Ambulatory function
KW - Duchenne muscular dystrophy
KW - Genetics (clinical)
KW - Latent class trajectory analysis
KW - Natural history
KW - Neurology
KW - Neurology (clinical)
KW - Pediatrics, Perinatology and Child Health
KW - Variability
KW - Ambulatory function
KW - Duchenne muscular dystrophy
KW - Genetics (clinical)
KW - Latent class trajectory analysis
KW - Natural history
KW - Neurology
KW - Neurology (clinical)
KW - Pediatrics, Perinatology and Child Health
KW - Variability
UR - http://hdl.handle.net/10807/93154
UR - http://www.elsevier.com/locate/nmd
U2 - 10.1016/j.nmd.2016.05.016
DO - 10.1016/j.nmd.2016.05.016
M3 - Article
SN - 0960-8966
VL - 26
SP - 576
EP - 583
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
ER -