title: Categorizing natural history trajectories of ambulatory function measured by the 6-minute walk distance in patients with Duchenne muscular dystrophy.
abstract: 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.
authors.affiliation: Paediatric Neurology Unit, Catholic University, Rome, Italy. Electronic address: eumercuri@gmail.com.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mercuri
authors.affiliation: Analysis Group, Inc., 111 Huntington Ave, 10th Floor, Boston, MA, USA; The TAP Collaboration, One Broadway, 14th Floor, Cambridge, MA, USA.
authors.forename: James Edward
authors.initials: JE
authors.lastname: Signorovitch
authors.affiliation: Analysis Group, Inc., 111 Huntington Ave, 10th Floor, Boston, MA, USA.
authors.forename: Elyse
authors.initials: E
authors.lastname: Swallow
authors.affiliation: Analysis Group, Inc., 111 Huntington Ave, 10th Floor, Boston, MA, USA.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Song
authors.affiliation: The TAP Collaboration, One Broadway, 14th Floor, Cambridge, MA, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ward
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005080:Exercise Test; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000145:classification* / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D012189:Retrospective Studies; D013256:Steroids / Q000627:therapeutic use; D016138:Walking
chemical_list: D013256:Steroids
keywords: Ambulatory function; Duchenne muscular dystrophy; Latent class trajectory analysis; Natural history; Variability