Survival in Duchenne muscular dystrophy in Australia: a 50 year retrospective cohort study

Abstract

Background: There is limited evidence describing the changing natural history of DMD in Australia.

Methods: This retrospective cohort study collated information on clinical management and disease milestones from medical records of males with DMD attending a paediatric hospital between 1973 and 2019 and linked this to information from two adult tertiary hospitals. Data were stratified by decade of birth and Kaplan Meier analyses were conducted to describe median time to key disease milestones.

Findings: The cohort included 356 individuals with DMD with year of birth ranging from 1958 to 2014 and median (interquartile range, IQR) follow up time from diagnosis of 10.5 (4.1, 15.7) years. Use of corticosteroids, angiotensin-converting enzyme inhibitors (ACE-I), echocardiography and respiratory support increased over time. Mean age of diagnosis decreased from 6.4 years in those born before 1970 to 3.4 years in those born 2010-2019. Median (IQR) survival increased over time from 18.2 (15.2, 20.4) years in those born before 1970 to 24.0 (20.3, 27.5) years in those born between 1990 and 1999. Increased life expectancy was observed in individuals using corticosteroids, ACE-I and respiratory support.

Interpretation: Survival in individuals with DMD has increased over the last five decades, likely due to changes in clinical management. Given the increased population surviving to adulthood, there is a need to enhance clinical services and surveillance to support neuromuscular disease in Australia, especially in transitional care and adult populations.

Funding: Independent Research Grant, Pfizer Australia.

Keywords: Cohort study; Duchenne muscular dystrophy; Natural history; Survival.

Fig. 1

Stacked bar graph illustrating proportion of DMD disease causing variant types by decade of birth. The n for each decade of birth represents the number of individuals with DMD with a known DMD disease causing variant.

Fig. 2

Stacked bar graph illustrating proportion of DMD isoforms maintained by decade of birth. The n for each decade of birth represents the number of individuals with DMD with a known DMD disease causing variant (missing n = 1 patient from 2010 to 2019).

Fig. 3

Kaplan–Meier plots describing time to key disease milestone stratified by decade of birth. Decades with >50% individuals with DMD with unknown events were excluded from the plots. Respiratory support refers to bilevel positive airway pressure or tracheostomy; cardiac dysfunction defined as fractional shortening <27%. Hashmarks on curves individual censoring events.

Fig. 4

Forest plot showing the probability of survival at age 20 for individuals with DMD born before 2000 across birth decades. The circle represents the probability of survival at age 20 years for each decade and the spikes represent the 95% confidence interval.

Fig. 5

Kaplan–Meier plots describing time to death stratifies by clinical management. Respiratory support refers to bilevel positive airway pressure or tracheostomy. ACE-I: angiotensin-converting enzyme inhibitors. Hashmarks on curves indicate individual censoring events. Shaded bands represent 95% confidence intervals.

Fig. 6

Kaplan–Meier plot describing time to loss of ambulation stratified by corticosteroid treatment. Hashmarks on curves indicate individual censoring events. Shaded bands represent 95% confidence intervals.