Online Self-Report Data for Duchenne Muscular Dystrophy confirms natural history and can be used to assess for therapeutic benefits

Abstract

To assess the utility of online patient self-report outcomes in a rare disease, we attempted to observe the effects of corticosteroids in delaying age at fulltime wheelchair use in Duchenne muscular dystrophy (DMD) using data from 1,057 males from DuchenneConnect, an online registry. Data collected were compared to prior natural history data in regard to age at diagnosis, mutation spectrum, and age at loss of ambulation. Because registrants reported differences in steroid and other medication usage, as well as age and ambulation status, we could explore these data for correlations with age at loss of ambulation. Using multivariate analysis, current steroid usage was the most significant and largest independent predictor of improved wheelchair-free survival. Thus, these online self-report data were sufficient to retrospectively observe that current steroid use by patients with DMD is associated with a delay in loss of ambulation. Comparing commonly used steroid drugs, deflazacort prolonged ambulation longer than prednisone (median 14 years and 13 years, respectively). Further, use of Vitamin D and Coenzyme Q10, insurance status, and age at diagnosis after 4 years were also significant, but smaller, independent predictors of longer wheelchair-free survival. Nine other common supplements were also individually tested but had lower study power. This study demonstrates the utility of DuchenneConnect data to observe therapeutic differences, and highlights needs for improvement in quality and quantity of patient-report data, which may allow exploration of drug/therapeutic practice combinations impractical to study in clinical trial settings.

What can Duchenne Connect teach us about treating Duchenne muscular dystrophy?

“…Both are shown to be effective in slowing disease progression modestly [22]. Interestingly, Cox analysis of DuchenneConnect participants found hazard ratios (HR) for deflazacort more protective than prednisone (HR 0.2 and 0.4 respectively) [11]. This finding differs from an earlier but underpowered study of 18 boys [23] and agrees with a subsequently and recently published study of 340 participants [24].…”

“…Interestingly, even controlling for the large effect of steroids, boys using Coenzyme Q10 or Vitamin D were observed to have a delay in age at loss of ambulation suggesting some small therapeutic effect. Coenzyme Q10 benefit was noted by a recent CINRG study [26], but the effect of Vitamin D is novel and the benefit appeared unrelated to a decrease in bone fractures [11]. This illustrates the benefits of aggregating individual data for seeding ideas for future clinical trials.…”

“…Over 10,000 individuals with DMD are expected to exist in the United States [9,10] and less than 20% of that population has registered with DuchenneConnect or participated in a clinical trial or research study [11]. This is an outstanding sampling of the US DMD population nonetheless.…”

“…Prolonged age at loss of ambulation, defined as the age at which a boy requires full time wheelchair use, was highly correlated with use of either deflazacort or prednisone (N=633) by a median of three years as compared to steroid naïve boys (N=280) with P<0.0001 [11]. The hazard ratio of 0.35 for corticosteroid use as a predictor of age at loss of ambulation agrees well with other studies using the 6 minute walk test illustrating the robustness of the DuchenneConnect data despite its patient entered information.…”

Prevalence and Genetic Profile of Duchene and Becker Muscular Dystrophy in Puerto Rico

“…In Canada, 74% of patients had genetic testing performed for their diagnosis (19). A recent study in DMD patients in the USA cites that 94.7% of their reported population had genetic testing available for analysis (20). Genetic testing can be costly for patients, and it is not usually covered by medical insurance, which could explain the low number of DNA studies available for analysis in our clinics.…”