Researchers say it is important to carefully assess the timing of the start of corticosteroid treatment for Duchenne muscular dystrophy (DMD) in children and its potential association with disease outcomes.
The study, “Associations between timing of corticosteroid treatment initiation and clinical outcomes in Duchenne muscular dystrophy,” was published in the journal Neuromuscular Disorders.
DMD is an inherited childhood-onset disease characterized by mutations in the DMD gene that provides instructions for making a protein called dystrophin, located primarily in skeletal muscles used for movement and in the heart muscle. These mutations lead to progressive muscle weakness.
Many children with mutated DMD lose their ability to walk by age 13. In the U.S. in 2010, the prevalence of Duchenne’s was estimated to be around 1.4 per 10,000 boys ages 5 to 9 and 1.02 per 10,000 boys ages 5 to 24. The life expectancy for patients with DMD has been extended due to pharmacological treatment and clinical advances in cardiac and respiratory care.
Corticosteroids and angiotensin-converting enzyme (ACE) inhibitors, which help relax blood vessels, are the most frequently used therapies to modify disease progression in DMD patients.
However, the long-term benefits and risks associated with the use of corticosteroids are unclear, and there are no standard guidelines for when to begin treatment. As a result, the long-term effectiveness of corticosteroids according to when treatment was initiated, mainly in early childhood, has not been well studied.
To address this issue, the authors analyzed the associations between corticosteroid treatment and timing of treatment initiation and five clinical outcomes — age at loss of ambulation; ages at onset of cardiomyopathy, scoliosis, first fractures, and pulmonary function — among males with DMD from the population-based Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet).
MDSTARnet is a multi-state research network effort originally funded in 2002 by the Centers for Disease Control and Prevention (CDC). There are surveillance sites in Arizona, Colorado, Iowa, western New York state, South Carolina, and the Utah-Nevada region. Georgia recently joined the network.
The population-based surveillance program retrospectively identified and prospectively followed cases of Duchenne and Becker muscular dystrophy (DBMD) patients born from Jan. 1, 1982, to Dec. 31, 2011, who were diagnosed by age 21 and resided in one of the surveillance areas.
The authors analyzed 726 cases from the surveillance sites. Of these cases, 343 (47.3%, 301 definite and 42 probable) cases did not receive any corticosteroid treatment, 67 (9.2%, 66 definite and 1 probable), and 316 (43.5%, 296 definite and 20 probable) started treatment in early and late childhood, respectively.
The authors found that people with Duchenne’s who started corticosteroid treatment early, at the age of 5 or younger, were more likely to have earlier onset of cardiomyopathy (heart disease) and had a higher risk of a fracture compared to those who initiated treatment in late childhood — older than age 5 — or those without any treatment.
The individuals who began treatment earlier also showed overall decreased respiratory function when compared with patients in the late childhood treatment group. For all outcomes examined, the differences observed between the non-treated and late childhood groups were not statistically significant.
The authors acknowledge several limitations to the study. For example, there were no discriminations made between the the early and late childhood treatment groups for data analysis drug type, dosage regimen, and dosing intervals.
“Because corticosteroids remain a treatment of choice for DMD, continued, careful assessments of the timing of initiating of this treatment are needed. Our study can be a valuable reference for these future studies,” the authors concluded.