From the first work by Drachman et al. that recognized a benefit from corticosteroids1 in boys with Duchenne muscular dystrophy through the excellent randomized controlled trials (RCTs)2-5 of the 1980s and 1990s, the recognition that daily corticosteroids benefit boys with Duchenne muscular dystrophy is clear. More than forty years of work with hundreds of boys have demonstrated that corticosteroids prolong walking and improve the strength of boys with Duchenne muscular dystrophy. Deflazacort, available in Canada and Europe, is not approved by the U.S. Food and Drug Administration (FDA) for use in the United States. However, there are extensive long-term positive data showing that it is effective in boys with Duchenne muscular dystrophy6,7. Although weight gain with deflazacort is less than that with daily prednisone, other side effects, including loss of height, loss of bone density, and cataracts, do occur. The study by Lebel et al. clearly adds to these data with, to our knowledge, the longest continual follow-up of a treated cohort. However, the known side effects have led to many alternative regimens and drug formulations. Intermittent corticosteroid dosing regimens, including the twice-weekly or alternate-day regimens, show promise in minimizing side effects8-10, but long-term follow-up is not yet available.
Despite this extensive body of evidence, many boys with Duchenne muscular dystrophy are never offered corticosteroids because of known side effects. To try to address this discrepancy of care, a practice parameter was published by the American Academy of Neurology in 200511. Diagnostic management recommendations were agreed upon in an effort funded by the Centers for Disease Control and Prevention (CDC) to improve care12.
The present work by Lebel et al. clearly demonstrates that daily deflazacort prolongs life, delays deterioration in pulmonary function, and decreases the need for scoliosis surgery. This is a follow-up study of fifty-four boys who had been diagnosed with Duchenne muscular dystrophy. While still walking, they were enrolled in a nonrandomized comparative study of the glucocorticoid deflazacort. Thirty boys (56%) received glucocorticoid treatment, a decision made by their families and physicians. In this study, Lebel et al. defined scoliosis as a Cobb angle measurement of >20° on posteroanterior radiographs. Six (20%) of thirty boys in the glucocorticoid treatment group and twenty-two (92%) of twenty-four boys in the non-treatment group developed scoliosis and underwent spinal surgery. Some of the same authors from the study by Lebel et al. also recently published a study of a similar experience in which boys with Duchenne muscular dystrophy who had a daily dose of 0.9 mg per kilogram had a rate of scoliosis (also defined as >20°) of 27% (ten of thirty-seven)13. In both reports, the positive effect of corticosteroid treatment is clear.
All daily corticosteroids, either in the form of deflazacort or prednisone, have long-term consequences. The major side effect was cataracts, which developed in 70% of the treatment group, but required surgical treatment in only two of those twenty-one boys. Finally, the loss of linear growth was apparent as the treatment group measured 17 cm shorter with regard to mean height. The treatment group also had a higher mean weight compared with the non-treatment group.
The severe side effects related to corticosteroid use may be minimized by differing dosing regimens. Yilmaz et al.10 demonstrated similarly striking results in their cohort of eighty-eight patients. Of these, sixty-six patients who were on an alternate-day corticosteroid treatment did not develop scoliosis, whereas seven of the twenty-two in the control group developed scoliosis at a mean follow-up duration of 2.75 years. Ultimately, the optimal dosing regimen that maximizes the benefits and minimizes the side effects of corticosteroids needs to be determined to promote its more widespread use.
Ideally, an RCT is the gold standard for proving efficacy of a medical intervention. The large effect size noted in multiple reports on the effect of corticosteroids on scoliosis means that powering a study with the appropriate sample size to answer this question would not be overly ambitious10,14. However, the compelling benefits in this study and others would suggest that RCTs should be used only to determine the appropriate dosage regimen, not to answer a treat or not-to-treat question.
This excellent study offers long-term prospective data that physicians can use to encourage more families and their physicians to try corticosteroids in patients with Duchenne muscular dystrophy. The recommendations by the collaborative group also allow practical advice for adjusting dosing and ensuring that 100% of boys at least try corticosteroids in some form12.