Five Common Corticosteroid Questions and Considerations

Corticosteroids are anti-inflammatory drugs that play an important role in treating some neuromuscular diseases. These medications are the fastest and most efficient way to control inflammation, and they can also reduce pain and suppress overactive immune system responses.

According to Elizabeth McNally, MD, PhD, a cardiologist and Director of Northwestern University’s Center for Genetic Medicine in Chicago, corticosteroids “are used to slow disease progression and reduce inflammation-mediated muscle damage, especially in genetic muscular dystrophies and autoimmune myopathies.”

The trade-off is a range of side effects — some of which are serious.

When you’re prescribed corticosteroids, it’s important to ask questions and consider all the ways they could impact your health.

What are corticosteroids and how are they used?

Corticosteroids are a class of steroids that target inflammation, a cause of muscle damage and weakness. They work by mimicking cortisol, a hormone produced by the adrenal glands. Cortisol helps regulate the body’s stress response and limits inflammation when used in short bursts.

Corticosteroids are primarily prescribed as a first-line treatment for Duchenne muscular dystrophy (DMD), for which there’s the most extensive data on long-term risks and benefits. When used for DMD, they can slow the rate of muscle weakness, improve cardiovascular health, and slow the rate of decline in ambulation (ability to walk).

They may also be prescribed off-label for other forms of muscular dystrophy that involve inflammation, such as Becker muscular dystrophy (BMD) and facioscapulohumeral muscular dystrophy (FSHD), but studies have not shown them to be as effective for these conditions.

Because corticosteroids suppress the immune system, they also may be prescribed for autoimmune neuromuscular diseases, including myasthenia gravis, Lambert-Eaton myasthenic syndrome, inclusion body myositis, polymyositis, and dermatomyositis. In these conditions, corticosteroids help lessen symptoms.

Are there options besides prednisone?

There are three FDA-approved corticosteroid options: prednisone, deflazacort (Emflaza), and vamorolone (Agamree).

• Prednisone is a pill that has been in use for more than 70 years across a wide variety of diseases, including those beyond neuromuscular diseases. Its usage for neuromuscular diseases is on an off-label basis.
• Emflaza (deflazacort) is a derivative of prednisone, was approved by the FDA in 2017 and is available in tablet and oral suspension forms. Emflaza is indicated for the treatment of DMD in patients 2 years of age and older.
• Agamree (vamorolone)is an oral suspension approved in 2023 for the treatment of DMD in patients 2 years of age and older. It has anti-inflammatory benefits with fewer side effects than its predecessors.

“The studies comparing vamorolone to prednisone show that bone growth was significantly better in boys taking vamorolone compared to prednisone,” Dr. McNally says. “This is a clear benefit for boys with DMD.”

Agamree received early funding through MDA’s Venture Philanthropy program.

What are the risks of taking corticosteroids?

Although corticosteroids are effective therapies, they have serious side effects when taken long-term, including:

• Effects on blood sugar. “Taking corticosteroids stimulates an increase in blood sugar and insulin,” Dr. McNally says. “This can mimic the early phases of diabetes. Over months and years, this leads to obesity, bone loss, and cataracts.”
• Weight gain. Corticosteroids often lead to weight gain, which can make mobility more difficult. Proper nutrition, therefore, is imperative. Dietitians who are part of the MDA Care Center team can work with patients to develop a healthy eating plan to manage this symptom.
• Stunted growth. Long-term corticosteroid use in children and adolescents can affect growth hormones and bone formation, inhibiting their growth potential. Agamree has been noted to cause less stunted growth or weight gain than prednisone or Emflaza.
• Bone loss and osteoporosis. Long-term corticosteroid use can cause bone loss, which can lead to osteoporosis, a condition that makes bones weak, brittle, and prone to fractures. To offset this risk, patients may be prescribed calcium or vitamin D supplements. To monitor bone loss over time, a DEXA scan (bone density test) and X-rays can be taken annually. Many MDA Care Center teams have affiliated endocrinologists or orthopedists who are familiar with corticosteroids and their impacts on bone health.
• Mental and behavioral health issues. Corticosteroids have been known to cause or exacerbate mental health issues. “The most common are mood disturbances like irritability, anxiety, depression, euphoria, and mood swings,” Dr. McNally says. “In children, this can be seen as hyperactivity and appearing stimulated. Insomnia and disrupted sleep can also occur.”
• Lower testosterone. Long-term corticosteroid use also leads to reduced testosterone levels. “It is important to follow testosterone levels and consider treating low testosterone if it is present,” Dr. McNally says. “Anyone beyond puberty can show signs of low testosterone, which can cause increased fat mass and lower muscle mass. Judging low muscle mass in the face of muscular dystrophy is really difficult, if not impossible, since muscular dystrophy causes low muscle mass. This is why testosterone is measured in the blood.”
• Long-term effects on the adrenal and immune systems. Long-term corticosteroid use can raise the risk of severe side effects, including death, if the dose is too low in certain situations.

“Taking corticosteroids every day leads to suppression of the body’s own adrenal function,” Dr. McNally says. “This can be a problem when the body is placed under stress and cannot respond to that stress by naturally increasing cortisol production. This acute adrenal insufficiency can be life-threatening and can be treated by giving higher doses of steroids.”

In the last decade, efforts have been made to establish guidelines on how to taper off corticosteroids and manage stress dosing. PJ’s Protocol was developed after the tragic loss of PJ Nicholoff, who died of an adrenal crisis.

Is there any new research on corticosteroids?

Research into corticosteroids is ongoing.

One particular avenue of interest is adjusting the dosing of current therapies to maximize benefits while mitigating side effects. “Our group has been very interested in intermittent dosing of prednisone,” Dr. McNally says. “We tested using prednisone just once a week in animal models with different forms of muscular dystrophy, including two forms of limb-girdle muscular dystrophy, and we found substantial benefit. We did a small pilot trial in people with limb-girdle muscular dystrophy, suggesting once weekly steroids could be a useful strategy.”

Another area of study involves using biomarkers to fine-tune steroid dosing and optimize benefits, as steroids are metabolized differently from person to person. Biomarkers are defined by the NIH as “a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition.”

Says Dr. McNally: “We studied multiple biomarkers including many proteins measured as aptamers, insulin, cortisone, branched chain amino acids and others.”

How do I know if corticosteroids are right for me?

If you are prescribed corticosteroids for a neuromuscular disease, discuss the potential benefits, side effects, and risks with your care team.

“This is a conversation to have with your doctor,” Dr. McNally says. “Nearly all children with DMD are offered steroids. It is a more open question in BMD and other forms of muscular dystrophy, where we do not have as much data.”

If you are taking corticosteroids and have concerns or notice any worrisome symptoms, don’t hesitate to speak up, especially regarding mental health. “If there are any sudden changes in mood or behavior, it is a good idea to discuss this with your doctor,” Dr. McNally says. “You should not stop or change medications without talking with your doctor.”