OBJECTIVES:

This study sought to characterize changes in disease burden and physical functioning before and following LoA among boys with DMD, and compare these changes by age at LoA (AaLoA).

METHODS:

Boys with LoA (self/parent-reported full-time wheelchair use) were identified from the CINRG Duchenne Natural History Study and divided into three AaLoA groups (<10 years, 10-13 years, >13 years). Major Adverse Dystrophinopathy Events (MADE) and Quantitative Muscle Testing (QMT) grip scores, and counts and proportion of patients who used a wheelchair/walker daily and less than daily, were calculated at 6-month intervals, from 5 years pre- to 5 years post-LoA, overall and by AaLoA group.

RESULTS:

Among 165 patients with LoA data, mean (standard deviation [SD]) age at enrollment was 11.0 (3.6) years (n=45: AaLoA <10 years; n=45: 10-13 years; n=32: >13 years). Across groups, MADE scores increased over time, particularly around 2 years pre-LoA; burden was generally higher with later AaLoA (mean [SD] MADE score at LoA <10 years: 14.1 [6.9]; 10-13 years: 15.8 [7.0]; >13 years 17.4 [5.8]). Among those with AaLoA <10 years, wheelchair use was observed from 2 years before LoA, progressing to >50% having wheelchair use, including daily use, ≤6 months pre-LoA. Among those with AaLoA >13 years, wheelchair use started 5 years before LoA, progressing to >90% having daily wheelchair use ≤6 months pre-LoA. QMT grip strength score peaked 2-3 years pre-LoA, then decreased over time, across all groups.

CONCLUSIONS:

In DMD, LoA represents an important marker of disease burden and physical functioning, in a gradual course of progressive decline. Patients with earlier AaLoA progressed to fulltime wheelchair use faster from initiation of wheelchair use. Despite limited data availability, observed trends suggest that therapies that slow progression to LoA may also address the worsening burden and functioning in DMD regardless of timing of LoA.