The study, “Cardiorespiratory Progression Over 5 Years and Role of Corticosteroids in Duchenne Muscular Dystrophy: A Single-Site Retrospective Longitudinal Study,” was published in the journal Chest.
Treatment with corticosteroids is the standard approach for DMD, regardless of underlying mutations. Their efficacy in preserving respiratory function is still an open question, with prior studies reporting contradictory results. Likewise, the extent of benefit in halting the progression of cardiomyopathy — cardiac muscle disease — remains an unresolved question.
Researchers with the Dubowitz Neuromuscular Centre at the UCL Great Ormond Street Institute of Child Health, in the U.K., led a study investigating how the two most common corticosteroid regimens — daily or intermittent use — as well as the two most frequent DMD therapies, prednisolone and Emflaza (deflazacort, marketed by PTC Therapeutics), affected heart and lung function in children with Duchenne.
They analyzed the medical records of 270 boys, with a mean age of 6.2 when they began regular care at the center. Sixty-six boys were treated with corticosteroids daily, 182 took them intermittently (10 days on and 10 days off), and 22 had never used corticosteroids (treatment-naïve). All treated boys were on corticosteroids for more than one month.
Of them, 204 boys were taking prednisolone and 36 were using Emflaza for at least 60% of the treatment period. All patients were followed for an average of 5.6 years.
Regardless of the treatment regimen, lung function decline — measured by forced vital capacity percent (FVC %) predicted — started at about age 9 and declined by an average of 6.1% per year. Those who were treatment-naïve declined at a rate of 4.7% per year, which was not statistically different compared to the treated groups.
Boys taking corticosteroids daily had significantly better lung function (90.8%) before the decline, compared with those receiving intermittent treatment (83.9%).
Patients on either daily or intermittent regimens reached FVC % predicted of less than 50% at a similar age, about 16 years old. This was almost three years later than the treatment-naïve group (median age, 13.2).
“All these results suggest that CSs [corticosteroids] delay the onset of respiratory decline … but do not slow down its progression once decline has started,” the scientists wrote.
Treatment-naïve patients required non-invasive ventilation at a median age of 15.7, which was earlier than treated patients. In fact, less than 25% of boys on corticosteroids required such breathing support by age 18.
The median age when lung function declined to less than 50% was significantly lower in boys treated on Emflaza (15.4 years) than those treated with prednisolone (16.8 years).
No difference in decline in heart function was seen between the two treatment regimens, with a yearly decrease of 0.53%. In contrast, boys in the treatment-naïve group declined by 1.17% per year, faster than treated patients.
The median age at cardiomyopathy was 16.6 years in the corticosteroid-treated groups, which was similar between regimens, and compared to 13.9 years in the treatment-naïve group. Patients using Emflaza developed cardiomyopathy later (most over age 18) compared to those on prednisolone (16.6 years).
Finally, a genetic analysis found that boys amenable to exon 44 skipping in the DMD gene had a slower decline in lung function (4.5% per year) compared to those with other genetic changes. Notably, being amenable to exon 44 skipping means having a mutation in this specific exon — one of the DNA bits containing information to make the dystrophin protein — and has been associated with better walking distance and slower decline than other genetic defects.
“Our data confirm the long-term beneficial effect of corticosteroids on respiratory and cardiac function in 270 patients with DMD, irrespective of regimen,” the scientists wrote.
They recommended further studies “to evaluate the differential role of CSs in older nonambulant [not able to walk] patients, particularly in view of the evidence for their positive effects on cardiac function,” they added.
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