Poster Number: 177


Alexis Mickle, MSc, Broadstreet Health Economics & Outcomes Research, Karissa Johnston, PhD, Broadstreet Health Economics & Outcomes Research, Kristen Ricchetti-Masterson, PhD, MSPH, Sarepta Therapeutics, Sarah Korpach, MPH, Broadstreet Health Economics & Outcomes Research, Katherine Gooch, Ph.D, MAppEpi, Sarepta Therapeutics

BACKGROUND: Becker muscular dystrophy (BMD) is caused by in-frame mutations in the DMD gene. Phenotype varies from asymptomatic to severe; manifestations may include development of cardiomyopathy, loss of ambulation (LOA), and respiratory insufficiency. This study aimed to characterize the frequency and age at occurrence of these milestones.
METHODS: A ‘living’ systematic review was refreshed in 2022 using MEDLINE and EMBASE to identify articles describing the natural history of BMD. Mean (standard deviation [SD]) age at occurrence of each milestone was reported, while the proportion experiencing each milestone was reported by ‘life-stage’ age groups of 0-17, 18-40, and 41+ years using patient-level data representative of the general BMD population.
RESULTS: From 4,958 abstracts screened, 186 articles were included. Mean age at symptom onset was 12.5 (10.3) years (n=971). Of the outcomes reviewed, cardiomyopathy was observed most frequently, with 30.8% (age 0-17), 50.0% (age 18-40), and 71.5% (age 41+) experiencing cardiac dysfunction/cardiomyopathy (n=43). Mean age at cardiomyopathy incidence was 32.2 (13.5) years (n=188). LOA was infrequently observed, with 8.6% (age 0-17), 14.8% (age 18-40), and 29.6% (age 41+) losing ambulation (n=223); for those who lost ambulation, this occurred at mean age of 33.5 (13.3) years (n=262). Requiring ventilation due to respiratory insufficiency was rare, and uncommonly reported in the literature, thus analyzing patient-level data was infeasible. The highest reported proportion from one publication was 15% requiring ventilatory support (n=13); mean age was 31.0 (2.6) years. Overall, mean age at ventilation initiation (non-invasive or invasive; n=21) was 35.2 (12.0) years.
DISCUSSION: In published studies of patients with BMD, many did not experience key clinical milestones. In patients for whom clinical events occurred, age at occurrence was variable. Cardiomyopathy was the most frequently manifestation of symptomatic BMD; respiratory insufficiency was rare. Ability to classify patients by distinct milestones was limited by heterogeneity in reporting.