Clinical Outcomes in Duchenne Muscular Dystrophy: A Study of 5345 Patients from the TREAT-NMD DMD Global Database

Abstract

Background: Recent short-term clinical trials in patients with Duchenne Muscular Dystrophy (DMD) have indicated greater disease variability in terms of progression than expected. In addition, as average life-expectancy increases, reliable data is required on clinical progression in the older DMD population.

Objective: To determine the effects of corticosteroids on major clinical outcomes of DMD in a large multinational cohort of genetically confirmed DMD patients.

Methods: In this cross-sectional study we analysed clinical data from 5345 genetically confirmed DMD patients from 31 countries held within the TREAT-NMD global DMD database. For analysis patients were categorised by corticosteroid background and further stratified by age.

Results: Loss of ambulation in non-steroid treated patients was 10 years and in corticosteroid treated patients 13 years old (p = 0.0001). Corticosteroid treated patients were less likely to need scoliosis surgery (p < 0.001) or ventilatory support (p < 0.001) and there was a mild cardioprotective effect of corticosteroids in the patient population aged 20 years and older (p = 0.0035). Patients with a single deletion of exon 45 showed an increased survival in contrast to other single exon deletions.

Conclusions: This study provides data on clinical outcomes of DMD across many healthcare settings and including a sizeable cohort of older patients. Our data confirm the benefits of corticosteroid treatment on ambulation, need for scoliosis surgery, ventilation and, to a lesser extent, cardiomyopathy. This study underlines the importance of data collection via patient registries and the critical role of multi-centre collaboration in the rare disease field.

Keywords: DMD; Duchenne muscular dystrophy; Neuromuscular diseases; TREAT-NMD.

Conflict of interest statement

All authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Professor Hanns Lochmüller was elected chair of the TREAT-NMD Alliance in April 2012. He and Jan Verschuuren both served as chairs of the oversight committee.

Figures

Fig.1

Overview of corticosteroid use within the global TREAT-NMD DMD database. Corticosteroid was reported as “corticosteroids yes” (current corticosteroid users/red bars), “corticosteroids never used ”(corticosteroids never used/green bars), “past corticosteroid use” (used corticosteroids in the past/blue bars) or “corticosteroid use unknown” (corticosteroid use unknown/orange bars”).

Fig.2

Turnbull analysis for loss of ambulation. The red line indicates the “corticosteroid yes” group, the green line the “corticosteroid no (never)” group and the blue line the “past corticosteroid use” group. P-value indicates the difference between the steroid: yes and steroid: no groups.

Fig.3

Assisted ventilation within the global TREAT-NMD DMD database.

Fig.4

Chi-square testing for scoliosis surgery (A), ventilation (B) and cardiomyopathy (C) in the patient group aged 20 years and older.

Fig.5

Turnbull analysis of loss of ambulation in patients under the age of 20 years, never (A) and ever (B) treated with corticosteroids and with a single exon deletion of exon 45 (red line), exon 51 (green line), exon 44 (purple line), exon 52 (black line) and exon 50 (blue line).

Fig.6

Turnbull analysis of loss of ambulation in patients under the age of 20 years in mutations rescued by exon skip 44 and 51. (A) represents patients never treated with corticosteroids and (B) represents patients ever treated with corticosteroids. In both figures the red line indicates patients with deletion of exon 45 mutation, the green line indicates patients with mutations amenable to exon skipping with exon 44 (but not deletion of exon 45 mutations), the blue line indicates patients with deletion of exon 50 mutation and the black line indicates patients with mutations amenable to exon skipping with exon 51 (but not deletion of exon 50 mutations).