PRO63 THE NATURAL HISTORY OF DUCHENNE MUSCULAR DYSTROPHY IN THE CORTICOSTEROID ERA: A SYSTEMATIC REVIEW OF STUDIES FROM CANADA AND THE US

Abstract

DMD is a severe progressive myopathy characterized by early loss of ambulation (LOA) and reduced life expectancy; and corticosteroids (CS) can delay disease progression. As new treatments emerge, understanding the CS-treated natural history is important. However, a synthesis of outcomes data is lacking. The objective was to summarize data on age at LOA and death from CS-treated patients with DMD. A systematic review was conducted using MEDLINE and EMBASE. This analysis focused on studies with a minimum sample size ≥50 CS-treated DMD patients from the US and Canada. Outcomes included mean or median age at LOA and death. From 5,637 abstracts, 14 studies reported on age at LOA, and 7 on age at death. Estimates of mean age at LOA, reported in 5 studies, ranged from 9.5 (% with LOA not reported (NR) in n=112) to 12.5 (LOA in 68% of n=75) years. Median age at LOA, reported in 10 studies, ranged from 12.0 (n=63) to 14.0 (n=94) years (% with LOA NR). Mean age at death, reported in 3 studies, ranged from 18.1 (in 11% of n=101) to 20.0 (in 13% of n=437) years. Mean age at death from 3 separate studies of ventilated and non-ambulatory patients ranged from 27.3 (n=25) to 30.4 (n=108) years (% deaths NR), and was 26.0 (47.4% of n=114) years in one study of DMD-related cardiomyopathy. Natural history studies among CS-treated patients from Canada and the US report that LOA on average occurs early in the second, and death in the third, decade of life. Limitations include: a) mean ages are reported from the subset experiencing the outcome; b) variable inclusion criteria reduce estimate comparability; and c) small sample sizes with short follow-up impact accuracy. As factors such as genotype variability are presently unaccounted for, meta-analysis may improve estimate precision.