24 Month Longitudinal Data in Ambulant Boys with Duchenne Muscular Dystrophy

Abstract

ObjectivesThe aim of the study was i) to assess the spectrum of changes over 24 months in ambulant boys affected by Duchenne muscular dystrophy, ii) to establish the difference between the first and the second year results and iii) to identify possible early markers of loss of ambulation.MethodsOne hundred and thirteen patients (age range 4.1–17, mean 8.2) fulfilled the inclusion criteria, 67 of the 113 were on daily and 40 on intermittent steroids, while 6 were not on steroids. All were assessed using the 6 Minute Walk Test (6MWT), the North Star Ambulatory Assessment (NSAA) and timed test.ResultsOn the 6MWT there was an average overall decline of −22.7 (SD 81.0) in the first year and of −64.7 (SD 123.1) in the second year. On the NSAA the average overall decline was of −1.86 (SD 4.21) in the first year and of −2.98 (SD 5.19) in the second year. Fourteen children lost ambulation, one in the first year and the other 13 in the second year of the study. A distance of at least 330 meters on the 6MWT, or a NSAA score of 18 at baseline reduced significantly the risk of losing ambulation within 2 years.ConclusionsThese results can be of help at the time of using inclusion criteria for a study in ambulant patients in order to minimize the risk of patients who may lose ambulation within the time of the trial.

DMD genotypes and loss of ambulation in the CINRG Duchenne natural history study

“…LoA is a clinically meaningful natural history milestone in DMD and a reliable overall indicator of the severity of disease progression. 6,7 It is strongly correlated with the longitudinal changes of functional measures commonly adopted as clinical trial endpoints, [34][35][36] but compared to these, it is less influenced by motivational factors. Furthermore, LoA predicts other major disease milestones such as the need for ventilatory support and survival.…”

Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy

“…Understanding of DMD disease progression as measured by 6MWT has increased in recent years with publications of natural history data14, 15, 16, 17, 18, 19 as well as placebo‐arm reporting from DMD trials 20, 21, 22. Published data support that on average, 6MWT distance is stable or increases in patients <7 years of age, whereas it declines in older patients 15, 17, 18, 23, 24. Evidence also suggests that DMD genotype may influence disease severity 25…”

Translational and Regulatory Challenges for Exon Skipping Therapies

“…For DMD recently results of natural history studies have been published (Goemans et al, 2013;Henricson et al, 2013a;Henricson et al, 2013b;Mazzone et al, 2013;McDonald et al, 2013a;McDonald et al, 2013b;Pane et al, 2014). This information should be useful to set inclusion criteria and select the group most likely to show clinical benefit over placebo.…”