Glucocorticoids Preserve Late-Stage Functional Abilities in DMD After Loss of Ambulation, Study Finds

Treatment with glucocorticoids after loss of ambulation (LOA) in patients with Duchenne muscular dystrophy (DMD) can preserve late-stage functional abilities, respiratory function, and cardiac function, according to a study published in the European Journal of Neurology.¹

DMD is a genetic condition that leads to progressive muscle atrophy and weakness in affected patients, with disease onset typically occurring in early childhood.² New standards of care in recent decades, including ventilatory support, glucocorticoid treatment, proactive cardiac intervention, and multidisciplinary care, have increased life expectancy for patients with DMD from 19 years in the 1960s to 24-28 years currently, the study authors explained.¹

These standards of care include glucocorticoid treatment during non-ambulatory stages and specify that older patients who are naive to glucocorticoids may still benefit from them. However, glucocorticoid use decreases following LOA and the optimal regimen in adults is not yet known.

Most individuals with DMD transition to adult care between ages 14-18, with the expectation being that the multidisciplinary and supporting treatments started at diagnosis will extend into adulthood.

Doctors planning DMD treatment | Image credit: OlegKachura - stock.adobe.com

“Informing adult services about specific clinical features of this group is essential for planning and delivery of appropriate care, impacting quality of life and survival,” the study authors wrote. “In our neuromuscular center, transition is within the same team; however, there are dedicated transition clinics for some specialties, such as respiratory clinics.”

The authors conducted the retrospective study to characterize the functional abilities, respiratory and cardiac status, and treatment of patients with DMD as they transition to adult care and in adult disease stages. The study also assessed the association between treatment with glucocorticoids after LOA and clinical outcomes in late-stage DMD.

A total of 112 patients with DMD were included in the study, with a mean age of 23.4 (± 5.2) years. The study period extended from first genetic diagnosis as early as July 1986 to last individual follow-up as late as July 2022. The authors noted that 86 patients (77%) were born prior to the year 2000 when more consistent standards of care were implemented, including routine glucocorticoid use.

At final assessment, 47.2% of patients were on glucocorticoids, with a mean prednisone dose of 0.38 (± 0.13) mg/kg per day and a mean deflazacort dose of 0.43 (± 0.16) mg/kg per day. Motor function limitations at age 16 years included use of a manual wheelchair (89.7%), standing (87.9%), transferring from a wheelchair (86.2%), and turning in bed (53.4%). Peak cough flow was less than 270 L/min in 77.5% of patients at age 16 years, and 53.3% of patients had a predicted forced vital capacity of 50% or less at 16 years. Additionally, 40.3% had a left ventricular ejection fraction of less than 50%.

Patients treated with glucocorticoids after LOA had a reduced risk and delayed time to onset of functional difficulties, including difficulty balancing in a wheelchair and loss of hand-to-mouth function. They also showed delayed time to a forced vital capacity percentage of predicted less than 30% and forced vital capacity of less than 1 liter, as well as a lower frequency of left ventricular ejection fraction less than 50%. Outcomes were similar with prednisone and deflazacort, and use of glucocorticoids was similar regardless of functional, respiratory, or cardiac status.

While the study was limited by its single-center nature and small sample size, the findings suggest larger studies are warranted to confirm the association between glucocorticoids and preservation of late-stage functional abilities.

“Glucocorticoids after LOA preserve late-stage functional abilities, respiratory and cardiac function,” the authors concluded. “It is suggested using functional abilities, respiratory and cardiac status at transition stages for adult services planning.”

Reference

1. Schiava M, Lofra RM, Bourke JP, et al. Functional abilities, respiratory and cardiac function in a large cohort of adults with Duchenne muscular dystrophy treated with glucocorticoids. Eur J Neurol. Published online March 31, 2024. doi:10.1111/ene.16267

2. Duchenne Muscular Dystrophy (DMD). Muscular Dystrophy Association. Accessed April 12, 2024. https://www.mda.org/disease/duchenne-muscular-dystrophy