Yearlong, MDA-supported study comparing two prednisone dosing schedules in Duchenne MD found similar benefits and side effects
A one-year, MDA-supported study comparing a weekend-only prednisone treatment schedule with a daily prednisone schedule in boys with Duchenne muscular dystrophy (DMD) has found that the two treatment regimens provide about the same benefits and have approximately the same side-effect profile.
Prednisone slows the progression of muscle weakness and prolongs walking in children with DMD. However, it's a corticosteroid drug that has many potential side effects, such as weight gain, slowing of growth, decreased bone density, behavioral changes, high blood pressure and high blood sugar, any of which can limit its use.
"These findings add to the body of evidence supporting the use of prednisone to maintain muscle strength in Duchenne muscular dystrophy," said neurologist Valerie Cwik, MDA's Medical Director and Executive Vice President for Research.
"In general, these two dosing regimens are approximately equivalent with respect to benefits and side effects in DMD for the relatively short term," Cwik said. "However, we don’t know if they will remain equivalent for the long term, particularly with regard to maintenance of strength and to side effects, such as weight gain and growth retardation."
She added, "Although corticosteroids have been in common use for DMD for more than a decade, we still have much to learn about these drugs for the treatment of this disease."
The results from this daily-versus-weekend prednisone study, with an accompanying editorial, were published online July 13, 2011, in Neurology. (See Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy for a summary of the scientific paper and a way to purchase the paper; and Weekend high-dosage prednisone: A new option for treatment of Duchenne muscular dystrophy to purchase the editorial.)
Diana Escolar, then at Children's Research Institute in Washington, D.C., received MDA support to direct the study, which was conducted at 12 centers through the Cooperative International Neuromuscular Research Group, or CINRG. (Escolar has since relocated to Kennedy Krieger Institute in Baltimore.)
Sixty-four boys ages 4-10 years old were randomly assigned to receive daily prednisone or a compressed, weekend-only prednisone dosing regimen for a year.
Neither the participants nor the investigators knew who was on which regimen. (Those in the weekend-only prednisone group were given look-alike placebos to take during the week.)
Those in the daily prednisone group received the drug at 0.75 milligrams per kilogram of body weight per day. Those in the weekend-only prednisone group took 10 milligrams per kilogram of body weight of prednisone on Saturdays and Sundays only. (One pound equals 0.45 kilograms.)
Preliminary results were announced for this study in April 2008 and suggested the weekend-only dosage regimen might provide the same benefits with some reduction in side effects, but full analysis of the results has not supported these early predictions.
The investigators tested muscle strength and various aspects of the participants' health at the start of the study and one year later.
The two groups showed approximately the same improvement in total muscle strength scores for the arms and legs after a year's treatment with either dosage regimen.
Side-effect profiles were virtually identical between the two groups after a year. There were no significant differences between the daily- and weekend-prednisone groups in height, weight, body mass index, blood pressure, blood sugar, bone density in the lumbar spine or behavior.
Prednisone and related corticosteroid medications, such as deflazacort (available in Canada and other countries but not in the United States), have been widely used to treat DMD since the 1990s.
Several studies have shown that corticosteroids prolong muscle function in this disease, but the mechanism by which they do so remains unclear, and the side effects of these drugs can be a barrier to their use.
In 2005, the American Academy of Neurology (AAN) published guidelines for corticosteroid use in DMD, suggesting an optimal dose of 0.75 milligrams per kilogram per day of prednisone or 0.9 milligrams per kilogram per day of deflazacort, with reductions in dosage if necessary because of side effects.
For more about corticosteroids in DMD, see the following stories from Quest, May-June 2007:
The new study gives doctors and families another option for prednisone treatment of DMD. (These results apply only to DMD and not to the use of prednisone in any other condition.)
"Most importantly," the investigators note, "the finding of equivalently effective but different dosing regimens with similar safety profiles provides clinicians treating patients with DMD with alternative therapeutic options that may aid some families to adjust to corticosteroid treatment, which is of proven benefit for prolonging ambulation [walking] in DMD."
Any change in medication regimen for DMD should be discussed with a physician specializing in neuromuscular disease.