Progression of Disease Burden Among Boys with Duchenne Muscular Dystrophy (DMD) According to Ambulatory Status and Age at Loss of Ambulation (LoA)

OBJECTIVES: DMD is an X-linked neuromuscular disease characterized by progressive muscle weakness. While LoA is commonly reported, disease burden is less well-characterized. This study aimed to characterize disease progression in boys with DMD according to ambulatory status and age at LoA (AaLoA).

METHODS: Boys with DMD and available data on ambulatory status were identified from the CINRG Duchenne Natural History Study and categorized into three AaLoA groups (<10 years, 10-13 years, >13 years). Major Adverse Dystrophinopathy Events (MADE) scores were calculated for each visit by summing across scoring items (missing items contributed 0 points), with higher scores indicating higher disease burden. MADE change per 1-year age increase was estimated using unadjusted and adjusted linear mixed models (LMM). Unadjusted LMM included parameters for age at visit, AaLoA group, and ambulatory status. Adjusted LMM further included fixed effects for age at diagnosis and cumulative glucocorticosteroid use at visit.

RESULTS: Among 290 included patients (2,599 visits), mean (SD) age at enrolment was 13.1 (5.6) years. While ambulatory, adjusted least-squares (LS) mean (95% confidence interval [CI]) MADE score change per 1-year age increase was 2.88 (2.40-3.35) for patients with AaLoA <10 years, 2.38 (2.01-2.75) for 10-13 years, and 1.86 (1.51-2.20) for >13 years. While non-ambulatory, adjusted LS mean (95% CI) MADE change per 1-year age increase was 2.95 (2.56-3.35) for patients with AaLoA <10 years, 2.45 (2.16-2.74) for 10-13 years, and 1.93 (1.55-2.31) for >13 years.

CONCLUSIONS: This analysis demonstrated that patients with later AaLoA had slower disease progression; progression also appeared slightly slower in the ambulatory compared to non-ambulatory period. Limitations included small sample sizes and missing LoA data or MADE score components for some patients (possibly underestimating burden); nevertheless, results were derived from a substantial number of visits. These findings suggest that therapies that delay LoA may also delay progression of DMD morbidities.