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.

Health profile of a cohort of adults with Duchenne muscular dystrophy

“…There are well-documented benefits of longterm corticosteroid use in DMD on improving functional milestones, delaying development of scoliosis and cardiomyopathy, delaying the need for respiratory support, and improving survival and quality of life, [23][24][25][26] and there is a growing consensus recommending continued use of corticosteroids after loss of ambulation. 2,4 Recently, increased evidence has shown that the type of steroid 27 (prednisone or deflazacort) and the specific regimen 28 (daily vs. intermittent), as well as age at initiation 29,30 and duration of treatment, 31 all have a differential impact on individual clinical milestones.…”

Myogenesis modelled by human pluripotent stem cells uncovers Duchenne muscular dystrophy phenotypes prior to skeletal muscle commitment

“…In this recessive X-linked monogenic disorder, mutations in the DMD gene lead to the loss of a functional dystrophin protein, resulting in a progressive - yet severe - muscle wasting phenotype (1). In patients, symptoms usually appear in early childhood (2-5 years old) and worsen with age, imposing the use of wheelchair before 15 and leading to premature death by cardiac and/or respiratory failure(s) mostly around 30 years of age (2).…”

Developmental Pharmacodynamics and Modeling in Pediatric Drug Development

“…Fortunately, natural history studies are facilitating a definition of predictive clinical end points and biomarker development. Studies of hundreds of patients in international collaborative studies aim to identify early sensitive and reliable outcome measures that are predictive of later quality of life changes — these are then strong PD end points …”

“…Studies of hundreds of patients in international collaborative studies aim to identify early sensitive and reliable outcome measures that are predictive of later quality of life changesthese are then strong PD end points. 29,30 In eosinophilic esophagitis, the pathophysiology of the disease is similar in adults and children, and one of the main treatment goals of eosinophilic esophagitis is to reduce symptoms. 31 However, variable symptomatology across pediatric and adult populations complicates the development of instruments to measure both patient-and observer-reported outcomes.…”