Some interesting findings about prednisone’s effect on behavior in DMD, and on drugs that may alter its usage in myasthenia gravis, were part of the 61st annual meeting of the American Academy of Neurology (AAN), held recently in Seattle.
Daily prednisone led to better behavior than weekly, high-dose prednisone
Researchers obtained a somewhat surprising result regarding moderate-dose, daily prednisone versus high-dose, weekend-only prednisone in boys with Duchenne muscular dystrophy (DMD), according to a study by a team from Children's National Medical Center in Washington (CNMC) and the University of Pittsburgh.
The study, which was supported by MDA and the National Institutes of Health, found behavioral side effects associated with prednisone lessened over the course of a year in the daily prednisone group but stayed the same in the weekends-only prednisone group.
Twenty-eight boys with DMD were randomly assigned to receive 0.75 milligrams per kilogram of body weight of prednisone daily, while another 28 were randomly assigned to receive 10 milligrams per kilogram of prednisone weekly over two consecutive days (the weekend).
The investigators administered the Child Behavior Checklist (CBCL) rating scale at screening and after one, three, six, nine and 12 months.
Total behavioral problems at the start of the study were similar between the two treatment groups. One month into treatment, there were no changes in behavior within the weekend prednisone group and an improvement in total problems and attention in the daily prednisone group.
After a year, there were no significant differences within the weekend group. However, in the daily prednisone group, there were significant decreases in total problems, such as attention and aggression. The daily group also showed significantly fewer behavioral problems than the weekend group at one year.
At last year’s AAN meeting, researchers announced analyses of other aspects of this study. (See Prednisone.) At that time, they said the effects on maintenance of strength of the daily and weekend prednisone dosing schedules were similar, but that the time required to rise from the floor was better in the daily group.
Growth retardation, a side effect of predniosone, was less severe in the weekend prednisone group. Weight gain, another side effect, was the same in the two treatment groups after one year.
MYASTHENIA GRAVIS STUDIES
Some studies examined alternatives to long-term, high-dose prednisone. Prednisone, a corticosteroid drug that suppresses parts of the immune system, is often prescribed for this type of MG, and is fairly effective at helping patients maintain strength. However, it has many side effects, such as weight gain, high blood pressure, diabetes, bone loss and psychological problems, if taken for long periods of time at high doses.
Mycophenolate mofetil allowed patients to decrease prednisone
Michael Hehir at the University of Virginia Health System in Charlottesville, and colleagues, found that a drug called mycophenolate mofetil (CellCept), when added to prednisone or substituted for prednisone, enabled people with MG to reduce or eliminate their prednisone intake during the second and third years of their therapy.
There were 103 people in this study, all of whom had the type of autoimmune MG in which the acetylcholine receptors are the target of the immune system. These receptors are on the muscle fibers and receive signals from nerve fibers.
Those treated with mycophenolate mofetil alone began to improve between six months and a year after starting the drug. In the group taking mycophenolate mofetil and prednisone, the prednisone dose decreased after a year of mycophenolate mofetil.
More than two years after starting mycophenolate mofetil, 53 percent of the patients were off prednisone entirely, and 74.5 percent were taking less than 7.5 milligrams per day (a low dose).
Methotrexate also allowed reduction in prednisone dosage
Faisal Raja at the University of Kansas Medical Center in Kansas City, Kan., and colleagues, found that eight people with MG tolerated an immunosuppressant medication called methotrexate (Rhematrex, Trexall), and four were able to reduce their prednisone dosage after an average of 8.7 weeks on methotrexate. No one experienced any methotrexate-related adverse events, but no one had an improvement in their functional scores.
In seven patients, the acetylcholine receptor was the autoimmune target. In one, it was a protein called muscle-specific receptor tyrosine kinase, or MUSK, which is needed at the junction of nerve and muscle fibers.
Prednisone prevented or delayed onset of generalized MG in people with ocular MG
Another study, conducted by Mark Kupersmith at Roosevelt Hospital and the New York Eye and Ear Infirmary in New York, found prednisone appeared to prevent -- or at least delayed -- the onset of generalized (all over the body) MG in people who only had ocular (eye-muscle) MG, and that it also controlled double vision resulting from ocular MG.
Eighty-seven people with ocular MG participated in this study, of whom 55 received prednisone and 32 did not.
Participants were followed for more than four years or until generalized MG developed. Generalized MG developed in seven (13 percent) of the 55 who took prednisone and in 16 (50 percent) of the 32 who did not. It typically appeared within a year in those not taking prednisone.
Double vision associated with ocular MG was present at the end of the study in 15 patients (27 percent) of the 55 who took prednisone and in 18 (57 percent) of the 32 who did not.
To read about AAN reports on ALS (amytrophic lateral sclerosis) research, see “Searching for Signs: Possible ALS biomarkers discussed at American Academy of Neurology meeting.”