6 Minute Walk Test in Duchenne MD Patients with Different Mutations: 12 Month Changes

Abstract

ObjectiveIn the last few years some of the therapeutical approaches for Duchenne muscular dystrophy (DMD) are specifically targeting distinct groups of mutations, such as deletions eligible for skipping of individual exons. The aim of this observational study was to establish whether patients with distinct groups of mutations have different profiles of changes on the 6 minute walk test (6MWT) over a 12 month period.MethodsThe 6MWT was performed in 191 ambulant DMD boys at baseline and 12 months later. The results were analysed using a test for heterogeneity in order to establish possible differences among different types of mutations (deletions, duplications, point mutations) and among subgroups of deletions eligible to skip individual exons.ResultsAt baseline the 6MWD ranged between 180 and 560,80 metres (mean 378,06, SD 74,13). The 12 month changes ranged between −325 and 175 (mean −10.8 meters, SD 69.2). Although boys with duplications had better results than those with the other types of mutations, the difference was not significant.Similarly, boys eligible for skipping of the exon 44 had better baseline results and less drastic changes than those eligible for skipping exon 45 or 53, but the difference was not significant.Conclusionseven if there are some differences among subgroups, the mean 12 month changes in each subgroup were all within a narrow Range: from the mean of the whole DMD cohort. This information will be of help at the time of designing clinical trials with small numbers of eligible patients.

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

“…Earlier analysis of the Italian DMD registry had suggested the potential for mutation type to affect disease progression 25. In the current analysis, patients amenable to exon skipping were shown to experience more rapid declines on 6MWT than those with mutations not amenable to exon skipping, a difference that was statistically significant at 36 months.…”

“…Selection based on these parameters is supported by recent reports indicating that the main variables impacting disease progression in ambulatory DMD patients as measured by 6MWT are age, genotype, 6MWT distance at baseline, and corticosteroid use 3, 16, 24, 25, 29. Given the data that support the effect of corticosteroid therapy on delaying disease progression in DMD,3 corticosteroid use at baseline was required for all patients in the eteplirsen‐treated as well as the control cohort.…”

“…It has been previously suggested that disease severity may be affected by mutation type,25 and multiple publications have demonstrated an age‐dependent change in disease trajectory, showing that when younger than 7 years, boys with DMD experience a steady increase in 6MWT distance, whereas boys aged ≥7 years experience progressive decline 15, 26. In the current study, the pooled historical control data set was analyzed to further elucidate the effect of mutation type and age on disease progression to further the field's understanding of DMD disease progression and to identify the most comparable patient subset for comparison to the eteplirsen‐treated cohort.…”

“…All patients in the 2 investigator‐initiated studies (historical control group) had a genetically confirmed diagnosis of DMD and met predefined entry criteria 25, 30. All eligible patients visiting the participating centers during the enrollment period were enrolled, supporting that the population analyzed represented an appropriate and unbiased control cohort of DMD patients.…”

Imagerie et spectroscopie par résonance magnétique nucléaire du muscle strié squelettique

“…On peut en distinguer trois catégo-ries : les outils fonctionnels, les biomarqueurs de fluides biologiques et l'imagerie. Les études fonctionnelles sont au premier plan, avec une variété de dispositifs et de protocoles, dont beaucoup sont optimisés pour la mesure de mouvements spécifiques, et d'autres visant plutôt à une éva-luation de l'activité globale du patient (Scott et al 2012 ;Mazzone et al 2012 ;Servais et al 2013 ;McDonald et al 2013 ;Mayhew et al 2013 ;Pane et al 2014 ;Mazzone et al 2014 ;Hogrel et al 2014 ;Decostre et al 2015 ;Lynn et al 2015 ;Seferian et al 2015a ;Seferian et al 2015b). Ces derniers outils font partie d'une nouvelle discipline en pleine expansion, l'actimétrie, et offrent un accès inédit à une éva-luation du patient dans son environnement personnel sur de longues périodes de temps.…”