Relationship between Loss of Ambulation (LoA) and Timing of Pulmonary Outcomes Among Boys with Duchenne Muscular Dystrophy (DMD)

OBJECTIVES: Pulmonary impairment is an important factor in DMD-related mortality and its relationship to other clinical milestones such as LoA is unclear. This study sought to describe the relationship between age at LoA (AaLoA) and timing of pulmonary outcomes in the CINRG DMD Natural History Study dataset.

METHODS: Boys with LoA (self/parent-reported full-time wheelchair use) and who were pulmonary-event-free at CINRG enrollment assessment were included. Number of patients experiencing a pulmonary event and estimated median time-to-event, stratified by AaLoA (<10, 10-13, >13 years), were analyzed using Kaplan-Meier plots and compared using the log-rank test. Outcomes of interest were forced vital capacity (FVC) <1 liter (L) and predicted FVC (pFVC) ≤30% and ≤60%.

RESULTS: Among 54 patients with AaLoA <10 years, 20 (37%) experienced FVC <1L at median (95% confidence interval) 19.0 years [18.2, NA]; in the 10-13 years group (108 patients/39 events; 36%) age-at-event was 22.6 years [21.9, 26.2]; in the >13 years group (84 patients/12 events, 14%), 28.3 years [26.0, NA; p<0.0001]. For pFVC ≤60%, among 38 patients with AaLoA<10 years, 27 (71%) had a median age-at-event of 13.5 years [12.3, 14.4]; in the 10-13 years group (70 patients/54 events, 77%) age-at-event was 14.6 years [14.1, 15.8]; in the >13 years group (70 patients/32 events, 46%), 18.0 years [17.5, 19.7; p<0.0001]. For pFVC ≤30%, in the <10 years group (53 patients/20 events, 38%) age-at-event was 18.1 years [17.0, NA]; in the 10-13 years group (100 patients/38 events, 38%), 20.8 years [19.6, 24.4]; in the >13 years group (83 patients/14 events, 17%), 25.7 years [24.0, NA; p<0.0001].

CONCLUSIONS: In this descriptive analysis, a pattern of later time-to-pulmonary-event with older AaLoA suggests a potential relationship between these outcomes. While further analysis addressing the impact of immortal time bias will be necessary, this analysis lends support to the value of delay in LoA.