A large, multi-center, international study to assess the long-term benefits of glucocorticoid treatment for Duchenne muscular dystrophy (DMD) concludes that it does preserve muscle strength and function as well as reduce the risk of death for patients.
The findings, published online in the Nov. 22 edition of The Lancet, provide clinicians with invaluable data on the long-term efficacy of a medication regime that has been used for years to treat the devastating neuromuscular disease, but never investigated with up to 10 years of follow-up.
“This long-term, follow-up study provides the most definitive evidence that the benefits of glucocorticoid steroid therapy in DMD extend over the entire lifespan,” said Craig McDonald, professor and chair of physical medicine and rehabilitation at UC Davis and lead author of the study. “Most importantly, patients with Duchenne using glucocorticoids experienced an overall reduction in risk of death by more than 50 percent.”
Researchers in nine countries, led in part by McDonald and a team at UC Davis Medical Center, used an innovative approach for assessing the progression of the disease, which is a rare but fatal genetic disorder that affects about 1 in 5000 people – mostly boys – worldwide. It usually becomes apparent in early childhood, as weakened skeletal muscles cause delays in milestones such as sitting and walking.
“We defined eight disease-related and clinically meaningful milestones that included a combination of timed-functional test performance and an upper extremity functional ratings scale,” said Erik Henricson, an assistant professor, associate director for clinical research and a co-author of the study. “Creating milestone groups enabled us to more precisely evaluate the loss of abilities across a DMD patient’s lifespan and thus establish with confidence the long-term positive benefits of glucocorticoids in DMD treatment.”
The researchers analyzed data from the Cooperative International Neuromuscular Research Group’s Duchenne Natural History Study, the largest DMD patient study over time, to identify whether or not the short-term benefits of glucocorticoids might extend into the long term. Data for 440 DMD males ages 2 to 8 years old included approximately 22 percent of whom had never taken glucocorticoids or had only taken the medications for less than one year. By analyzing data for patients who were given the medications for at least one year and up to 10 years, the long-term benefits became apparent.
“The glucocorticoid treatment for patients who received it for more than one year avoided the loss of our mobility milestones -- laying down to standing, climbing four stairs, and walking or running 10 meters – that affect the lower limbs by two to more than four years,” McDonald added, as he and colleagues compared the longer-term treatments with those boys who received medications for less than one year. In addition, McDonald noted that there appears to be an advantage to deflazacort in comparison to prednisone or prednisolone with regard to preserving functions across the lifespan.
DMD children usually become wheelchair users during their teens. As heart muscle is increasingly affected, the disease becomes life threatening and many patients die from heart failure in their 20s. Glucocorticoids are currently a standard part of care for most patients with DMD, with some physicians prescribing the medications as soon as patients are diagnosed.
The current study also showed that long-term glucocorticoid therapy delayed the loss of mobility milestones in upper limbs, such as hand function, performing a full overhead reach and raising the hands to the mouth.
Limitations in the study included an imbalance in the cohort size (22 percent in the group of no medications or medications for less than a year versus patients using the glucocorticoids for at least a year or more) and non-randomization, which carries the risk of bias because of potential differences in treatment protocols.
McDonald says the next steps in DMD research will focus on the different drugs with the class of steroid hormone medications to determine which treatment regimens might offer the most benefits, and how those benefits could differ with long-term use.
Other co-authors of the study were Richard Abresch and Nanette Joyce, UC Davis School of Medicine; Tina Duong, Stanford University; Fengming Hu, Avital Cnaan and Heather Gordish-Dressman, Center for Genetic Medicine, Children’s National Health System and the George Washington University School of Medicine and Health Sciences; Paula Clemens, University of Pittsburgh; and Eric Hoffman, Binghamton University’s School of Pharmacy and Pharmaceutical Sciences; and the CINRG Investigators.
The research in this study was supported by the U.S. Department of Education/NIDRR, H133B031118 and H133B090001; the U.S. Department of Defense, W81XWH-12-1-0417; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number R01AR061875; and the Parent Project Muscular Dystrophy.