DMD’s Course With Corticosteroid Use Examined in Review Study
With current corticosteroid use, people with Duchenne muscular dystrophy (DMD) typically lose their walking ability by their early teens, often need ventilation by their late teens, and usually survive until the third or fourth decade of life, according to a review study into the clinical course of DMD today.
The review, “The clinical course of Duchenne muscular dystrophy in the corticosteroid treatment era: a systematic literature review,” was published in the Orphanet Journal of Rare Diseases. It was funded by Sarepta Therapeutics, which markets three DMD treatments: Amondys 45, Exondys 51, and Vyondys 53.
Recent decades have seen substantial advancements in caring for people with DMD. In particular, the introduction of corticosteroids as part of standard treatment, which began in the 1990s, has helped to slow disease progression and improve survival.
In this study, a team that included researchers at Sarepta reviewed published scientific literature to better understand the course that DMD tends to run in the modern day. The investigators focused their review on studies that took place in North America, and observed boys with DMD who were treated with corticosteroids. In total, they assessed 29 relevant studies.
“A comprehensive systematic review was conducted to identify estimates of the age at key clinical milestones, and trajectories on relevant functional measures over time, among studies including North American patients with DMD,” the team wrote.
The review revealed that the average age at loss of ambulation for corticosteroid-treated boys with DMD varied from about 9 years to nearly 12 years of age. Overall, up to 30% of patients were unable to walk by age 10, while nearly 9 in 10 were unable to walk by age 15.
“Age at LOA [loss of ambulation] was the most widely reported with estimates available from many large studies,” the researchers reported, while “robust data on the timing of the onset of scoliosis-, cardiac-, pulmonary- and ventilation-related outcomes were less frequently presented, particularly from large longitudinal studies.”
Scoliosis (sideways curvature of the spine) that was severe enough to require surgical correction tended to occur in boys around age 14. Over half of patients had scoliosis by 15, and nearly three-quarters had scoliosis by age 20, in an analysis that looked at seven studies in total.
Average age at onset for cardiomyopathy — a condition where the heart muscles are unable to adequately pump blood throughout the body — was typically in the mid-teens, with a fair amount of variation among its 19 different studies. By age 25, almost all DMD patients had cardiomyopathy.
The average age at which patients required ventilation to help with breathing was typically in the late teens or early 20s, with some variation depending on the specific type of ventilation (e.g., invasive or not). Measures of both heart and lung function tended to be within normal ranges during childhood, then began to decrease starting in adolescence.
The mean age at death varied from the late teens to early thirties, depending on the specific population being looked at in 18 individual studies (e.g., with cardiomyopathy or not). In the overall population, mortality rates were about 16.2% by age 20, and about 44.2% to 56.8% by age 30.
“The findings of this review help summarize the likely timing of disease progression milestones for North American patients with DMD, and also highlight potential heterogeneity [variation] in timing observed both within and across study populations,” the researchers concluded.
“Additional studies on the ages at occurrence of other important DMD clinical milestones, and the relationships between short-term and long-term outcomes, will be valuable in the continuation of knowledge regarding disease progression in DMD,” they added.