New research published in JAMA recommends daily steroid doses for children with Duchenne muscular dystrophy (DMD), marking a significant change in how the disease is treated. University of Rochester Medical Center (URMC) neurologist Robert Griggs, M.D., and Michela Guglieri, M.D., with Newcastle University in the U.K., led the study, which was conducted by a global team of researchers dedicated to improving care for this fatal disease.
“Corticosteroids are likely to remain the main treatment for DMD for the foreseeable future and worldwide so it is critical that we establish a standard of care that is backed by scientific evidence,” said Griggs. “This study shows that health concerns over the daily use of corticosteroids are overstated and that there is a clear benefit in terms of improved motor and pulmonary functions. These findings clearly support the daily regimen over an intermittent one as an initial treatment for boys with DMD.”
DMD is a condition found almost exclusively in boys and characterized by muscle weakness, which appear at age 3-4 and progresses rapidly leading to significant disability. The symptoms eventually spread to the heart and muscles responsible for breathing, and the disease is often fatal by the time the boy reaches his late teens. An estimated 28,000 people in the U.S. suffer from the disease.
While corticosteroids prednisone and deflazacort are known to improve muscle strength and function in patients with DMD and have been a frontline treatment for years, there is currently no universally accepted standard for steroid use in DMD. A global survey of physicians who treat DMD found 29 different regimens, with the most common being ten days on and ten days off. This intermittent dosing regimen was put in place in an effort to limit the potential side effects associated with prolonged steroid use in children, such as weight gain, stunted growth, and loss of bone density.
The Finding the Optimum Regimen of Corticosteroids for DMD (FOR-DMD) study was launched in 2013 to compare daily and intermittent steroid use and establish, from clinical benefit and safety perspective, the most beneficial regimen for DMD patients. Griggs and Kate Bushby, M.D., with Newcastle University initiated the phase 3 clinical trial conducted through the Muscle Study Group, an international network of muscular dystrophy researchers that Griggs helped create in 1997 to advance clinical research in neuromuscular disorders, including DMD.
The new study recruited 196 boys with DMD at 32 research sites across North American and Europe and followed them for three years. Participants were assigned to three groups consisting of daily regimens of prednisone or deflazacort, or intermittent prednisone, and followed for three years. The researchers found that the daily regimens of both drugs significantly slowed disease progression as measured by strength testing and muscle function, as compared to the intermittent group. While the daily regimen increased side effects overall, there were minimal serious side effects.
The lead biostatistician for this study was Michael McDermott, Ph.D., and other URMC investigators include Kimberly Hart, Rabi Tawil, William B. Martens, Barbara E. Herr, and Mary Brown. Other investigators involved in study include Elaine McColl, Chris Speed, Jennifer Wilkinson and Michelle Eagle with Newcastle University, Janbernd Kirschner with University Hospital Frieburg, Germany, Wendy King with Ohio State University, Tracey Willis with the Robert Jones and Agnes Hunt Orthopaedic Hospital in the U.K. The FOR-DMD study was supported with funding from National Institute of Neurological Diseases and Stroke, the Muscular Dystrophy Association, the Parent Project for Muscular Dystrophy, PTC Therapeutics, Sarepta Therapeutics, and Santhera Pharmaceuticals.