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Population-based estimates of survival among individuals with Duchenne muscular dystrophy (DMD) living in the United States are lacking. It is also unclear whether the association between glucocorticoid use and all-cause mortality persists in the context of other common treatments (cardiac medication, cough-assist, bilevel positive airway pressure, and scoliosis surgery) observed to delay mortality. Among 526 individuals identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network, the estimated median survival time from birth was 23.7 years. Current glucocorticoid users had a lower hazard of mortality than non-users. Individuals who ever had scoliosis surgery had a lower hazard of mortality than individuals who did not have scoliosis surgery. Individuals who ever used cough assist had a lower hazard of mortality than individuals who never used cough assist. Non-Hispanic Black individuals had a higher hazard of mortality than non-Hispanic White individuals. No differences in hazards of mortality were observed between ever versus never use of cardiac medication and ever versus never use of bilevel positive airway pressure. The glucocorticoid observation is consistent with the 2018 Care Considerations statement that glucocorticoid use continues in the non-ambulatory phase. Our observations may inform the clinical care of individuals living with DMD.

Individuals with Duchenne muscular dystrophy (DMD) often exhibit delayed motor and cognitive development, including delayed onset of ambulation. Data on age when loss of independent ambulation occurs are well established for DMD; however, age at onset of walking has not been well described. We hypothesize that an effective medication given in early infancy would advance the age when walking is achieved so that it is closer to age-matched norms, and that this discrete event could serve as the primary outcome measure in a clinical trial. This study examined three data sets, Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet); Dutch Natural History Survey (DNHS); and Parent Project Muscular Dystrophy (PPMD). The distribution of onset of ambulation in DMD (mean ± SD) and median age, in months, at the onset of ambulation was 17.3 (±5.5) and 16.0 in MD STARnet, 21.8 (±7.1) and 20.0 in DNHS, and 16.1 (±4.4) and 15 in PPMD. Age of ambulation in these data sets were all significantly later (P < 0.001) than the corresponding age for typically developing boys, 12.1 (±1.8). A hypothetical clinical trial study design and power analyses are presented based on these data.

In preparation for a clinical trial to investigate the effectiveness of drug treatment in infants with Duchenne MD, a clinically meaningful primary outcome measure needs to be established. Our hypothesis is that infants with DMD have delayed age to walking independently, have an innate desire to walk as soon as the motor system permits this task, and that an effective drug for DMD would reduce the age when independent ambulation is reached. As such, age of independent ambulation is a discrete dichotomous event that may serve as an effective primary outcome measure in a clinical trial. The age when ambulation is first achieved was studied in 2 DMD population samples: US CDC MD STARnet (Dataset 1, 1982-present, n = 449) and a more historical Dutch natural history survey (Dataset 2, 1961–1982, n = 473) and compared to the WHO reference set in normal boys (mean ± SD [months, m], where walking was achieved at 12.1 ± 1.8 m, 99% by 17.6 m. The data were not normally distributed, possibly due to recall bias and rounding error. Age of ambulation in Dataset 1 was 17.0 ± 5 m and median age was 16.0 m, IQR 13.0, 18.0 with 96% walking by 24 months. In dataset 2, the mean age of ambulation was 21.8 ± 7.1 m and median age of was 20.0 m, IQR 18.0, 24.0 with 81% walking by 24 m. Based upon Data Set 1 there is a delay in walking among DMD boys of mean 4.9 m. A clinical trial design, with 1:1 randomization, power of 90% and alpha of 0.05, for a drug that shortens age at ambulation by 2 months, to a mean delay of 2.9 months, would require 86 boys in each arm if the SD is 4 and 23 boys in each arm if the SD is 2. Prospective data is necessary to obtain more secure data, especially for the mean/median and degree of variance. This information may be useful in preparation for newborn screening in DMD and having a clinical trial design that would capture a reliable clinically meaningful outcome measure independent of patient effort or evaluator bias.

Improved respiratory and cardiac management along with glucocorticoid therapy have contributed to increasing survival of patients with DBMD.This has led to a growing population of adults with DBMD. The purpose of this population based study was to describe the sociodemographic profile and health related outcomes of individuals with DBMD followed in the MD STARnet. MD STARnet is a multi state population based surveillance system that collects data on all individuals with DBMD born since 1/1/1982. In addition to epidemiologic data, MD STARnet collects extensive sociodemograhic and clinical data related to natural history milestones and treatments and services received by individuals with DBMD. The cohort for this analysis was all individuals born from 1/1/1982 to 12/31/1992 and followed through 8/31/2011. Overall, 384 individuals were identified of which 32% have died [mean age 17.6 years (8.7–25.5)], and 20% were lost to follow up [mean age 15.3 (0.9–25.8)]. The remainder continue to be followed [mean age 21.5 (17–28.6)]. Most individuals were white, non-Hispanic (59%) and live with parent/s/family (98%), have post high school/college training (24%). The number of individuals and the average age (range) at which they crossed clinical milestones or required specific treatments were as follows: loss of ambulation [ N = 300, 11.7 years (6.9–24.50)], scoliosis surgery [ N = 128, 14.7 years (10.3–20.2)], night time ventilator support [ N = 158, 16.9 years (9.4–26.2)], cardiomyopathy (SF N = 188, 16.5 years (9–25.5)], PEG [ N = 58, 19.2 years (11.8–26.0)]. Forty nine percentage have been treated with corticosteroids. Our population based data support an emerging population of adults with DBMD. This sociodemographic and health related profile provides information for providers, payors and policy makers to help design the appropriate care models for the needs of adults with DBMD and their families.