GROUPS PROBE
CORTICOSTEROID USE IN DMD
 

This spring, two groups published reports of their preliminary conclusions on the use of corticosteroids in Duchenne muscular dystrophy (DMD), with recommendations for further action.

Corticosteroids such as prednisone, its closely related compound prednisolone and the somewhat related compound deflazacort (not available in the United States) have been in common use for about a decade to prolong walking in DMD. However, there hasn’t been a consensus on the best dosage, age to start or criteria for stopping these powerful but potentially hazardous medications.

ENMC Report

A group of 35 participants from several European countries, the United States and Canada convened April 2-4 in the Netherlands to discuss new directions for corticosteroid use in DMD. Among them was Sharon Hesterlee, MDA’s director of Research Development.

In a report published in its entirety at www.enmc.org/workshops/reports.cfm?p=157, the group concluded that

• there can “no longer be any doubt that the use of steroids in ambulant [walking] children with DMD alters the natural history of the condition”
• children treated with daily steroids are likely to walk longer, have improved respiratory function, may avoid the need for spinal surgery and might have better heart function than untreated children
• there are significant side effects associated with the corticosteroids prednisone and deflazacort, most seriously weight gain and decreased bone density
• alternatives to daily steroids, such as steroids given every other day or for 10 days followed by 10 days off, or on weekends only, as well as different dosages, might mitigate side effects and still provide benefits
• a large-scale clinical trial to test the relative merits of different approaches to steroid use is urgently needed
• in advance of this trial, boys with DMD on steroids should be encouraged to be as active as possible and to maintain proper levels of vitamin D and calcium to avoid bone loss, as well as avoid sweets and fast foods to control their weight.

Cochrane Review

Also published this spring is the Cochrane Collaboration’s review of multiple studies of corticosteroids in DMD.

The Cochrane Collaboration is a not-for-profit international organization that publishes quarterly reports on health care interventions based primarily on analyses of randomized clinical trials -- those in which participants with the same characteristics are randomly assigned to a treatment or nontreatment group and then compared.

Summaries of these reviews are available at www.cochrane.org, and complete reviews are available for purchase through the Web site.

In Issue 2, 2004, of the Cochrane Library, the reviewers discuss corticosteroids for DMD, basing their analysis on five randomized trials.

Their analysis finds that

• corticosteroids improve or stabilize muscle strength and function for six months to two years
• the most effective dose of prednisone or prednisolone appears to be 0.75 milligrams per kilogram per day
• adverse effects, such as excessive weight gain, behavioral abnormalities, redistribution of body fat to the face and abdomen and away from the limbs, and excessive hair growth, are significantly more common in treated patients compared to untreated patients but aren’t severe
• the long-term benefits and hazards of corticosteroids in DMD can’t be evaluated from the currently published studies
• nonrandomized studies support the conclusions of functional benefits but also indicate significant adverse effects with long-term steroid treatment.

More studies are needed, the reviewers say.

MDA’s Role

MDA is supporting a study of high-dose, weekly prednisone compared to moderate-dose, daily prednisone being conducted at several sites across the country. For more information, contact study coordinator Erik Henricson at (202) 884-3813 or ehenricson@cnmcresearch.org.

A national clinical trials network, sponsored by MDA, will likely further investigate the use of corticosteroids in DMD. Groundwork for this network will be laid in June at a special MDA meeting.
 

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