Corticosteroid Use After Loss of Walking May Slow Lungs’ Decline in DMD

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by Steve Bryson, PhD |

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Continued use of corticosteroids beyond the year of losing an ability to walk can delay declines in lung function in boys with Duchenne muscular dystrophy (DMD), an analysis of MD STARnet data suggested.

In comparison, patients who never used corticosteroids or who discontinued treatment within one year of losing ambulation had an onset of lung function decline at younger ages. But no slowing in the onset of heart abnormalities was seen with longer-term use.

Further study of corticosteroids’ known risks and potential benefits in these patients may allow for better management of their continued use, the researchers noted.

The analysis, “Evaluation of effects of continued corticosteroid treatment on cardiac and pulmonary function in non-ambulatory males with Duchenne muscular dystrophy from MD STARnet,” was published in the journal Muscle & Nerve.

DMD is characterized by a genetically inherited deficiency in dystrophin, a protein that normally functions as an anchor to strengthen and protect muscles when they contract and relax. Its lack of leads to a shrinking and weakening of muscles required for body movement and, at later stages, heart muscles and those needed for breathing.

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Corticosteroids, also called glucocorticoids, are commonly prescribed to help preserve muscle strength by suppressing inflammation to delay the loss of ambulation (LOA), or independent walking.

“As patients with DMD progress beyond LOA, the relative importance of [corticosteroid] side-effects that were well-tolerated at earlier stages of disease increases, and management becomes more complex,” the researchers wrote. “Side effects such as weight gain, hypertension, and glucose intolerance … are compounded in non-ambulatory patients with active declines in heart and lung function.”

An earlier study, using data from the Muscular Dystrophy Surveillance, Tracking, and Research network (MD STARnet) — a U.S. surveillance program that collects information about muscular dystrophy — suggested that corticosteroid treatment in ambulatory and non-ambulatory DMD boys delayed the onset of cardiomyopathy, or heart muscle disease.

Researchers at the University of Utah and colleagues expanded on these MD STARnet findings to determine whether corticosteroid use, including prednisone and Emflaza (deflazacort), in non-ambulatory DMD boys was associated with a delayed onset of problems in heart and lung health.

An MD STARnet database search covering 30 years (1982–2012) identified 398 patients. Among them, 193 had never been prescribed corticosteroids, another 104 stopped their use within one year (before or after) of losing walking abilities, and 101 patients who began corticosteroids before losing walking abilities and continued treatment for another year or longer.

Left ventricular heart function was based on echocardiogram tests, while lung function was based on the percent predicted forced vital capacity (ppFVC), or the maximum amount of air forcibly exhaled compared with a predicted normal for the patient.

No difference in the age of onset of abnormal left ventricular function was found between non-ambulatory boys who continued with corticosteroids for at least another year and those who stopped this treatment or were never treated with corticosteroids.

Still, the time from ambulation loss to a first abnormal left ventricular measure “appeared to be shorter” in boys who continued being treated for one or more years than in those who stopped within a year of LOA or were never treated, the researchers noted. This difference, however, was not statistically significant across the groups.

“The shorter time from LOA to onset of abnormal LV function in boys for whom steroid treatment continued beyond LOA likely reflects prolonged ambulation in those individuals,” they wrote, “thereby creating a shorter interval between LOA and onset of abnormal LV function.”

A delay in lung function decline — determined as the average age at which the ppFVC dropped below 50% predicted — was seen in boys continuing with corticosteroids (onset at 15.98 years old). The average age of onset for the other two groups showed no significant differences, with at an average age at onset of 14.67 in boys who stopped therapy within one year and 14.96 for those never treated.

Risk of showing an abnormal ppFVC measurement was also higher in never-treated boys and those who discontinued within one year of LOA relative to those with continued corticosteroid treatment. That higher risk was only statistically significant between these latter two groups (stopping within one year versus continued use).

No statistically significant differences were evident between any of these groups in the mean time from the loss of ambulation to the first ppFVC measurement of less than 50% predicted.

Together, these results suggest “a benefit of delaying decline in lung function with corticosteroids, but this benefit may not persist beyond LOA,” the scientists wrote.

“Our findings highlight the complexity of treatment with corticosteroids for DMD and the importance of additional studies to determine the benefits and risks of prolonged treatment,” they added.

“Prospective studies [moving forward in time] of the effects of corticosteroids on motor, cardiac, and pulmonary function in non-ambulatory boys with DMD will be important in defining the risks and benefits to allow more effective counseling of patients about how long to continue treatment, and how and when to consider stopping treatment,” the investigators concluded.