Corticosteroid use in MG raises risk of developing other conditions

People with myasthenia gravis (MG) who take corticosteroids, especially at higher cumulative doses, face an increased risk of developing other health conditions, according to a study in the U.S.

Patients are at risk for conditions including diabetes, infections, and cardiovascular diseases, the researchers found.

“Our findings highlight the importance of individualizing therapy for patients with MG, and of considering the potential impact of comorbidities [simultaneous conditions] in treatment selection,” the researchers wrote. The data also “support the use of strategies that minimize the use of corticosteroids where possible in clinical practice.”

The study, “Impact of corticosteroid use on comorbidities in patients with myasthenia gravis in the US National Veterans Affairs Health Network,” was published in the Journal of the Neurological Sciences.

MG is caused by self-reactive antibodies that attack proteins involved in nerve-muscle communication, leading to MG symptoms such as muscle weakness and fatigue. People with MG often have comorbidities, including cardiovascular diseases, high blood pressure, diabetes, respiratory disorders, sleep conditions, depression, and other autoimmune diseases.

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Risks rise with age

“The prevalence of comorbidities among individuals with MG increases with age, and their presence can significantly increase the risks of MG exacerbations, hospitalization, and mortality, as well as impacting quality-of-life,” the researchers wrote.

Corticosteroids are anti-inflammatory medications widely used in MG to prevent the immune system from attacking healthy cells and tissues. Although they act rapidly to control symptoms, high doses and long-term use are associated with an increased risk of other health conditions.

To learn more, a team of researchers at Argenx and U.S. universities conducted a retrospective analysis of 1999-2024 electronic medical records from the National Veterans Affairs Health Care Network database.

Argenx develops and markets Vyvgart (efgartigimod alfa-fcab) and Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc), two therapies approved for certain types of MG.

The analysis covered 10,632 MG patients (average age 70.5, 95.7% men) and a similar number of people without the disease used as controls. Controls were matched as closely as possible to patients in terms of age, sex, race/ethnicity, region, and social deprivation index (a composite measure of socioeconomic disadvantage). Participants were followed for a mean of 7.8 years.

During follow-up, 84.5% of patients received at least one treatment, and 27.9% had three or more treatments. Corticosteroids were received by 51.6% of MG patients and 21.2% of controls. In the MG group, the mean daily corticosteroid dose was 19.2 mg, and these medications were given for a mean of 157.7 days (about five months) per year.

MG patients had significantly higher 10-year rates of all evaluated comorbidities — infections, cardiovascular disease, diabetes, depression, glaucoma, and osteoporosis — than those without MG. Glaucoma is a serious eye disease, and osteoporosis is a condition marked by weak, brittle bones.

In both the MG and non-MG groups, the risk of developing these comorbidities during follow-up was significantly higher in people treated with corticosteroids.

Among MG patients, further statistical analyses revealed an increased annualized risk, or that attributable to one year of corticosteroid treatment, of each of the six comorbidities with increasing annualized cumulative doses (dosage over one year).

An annualized cumulative dose below 1g was considered a low dose, between 1g and 5g a medium dose, and over 5g a high dose.

The researchers observed a significantly higher risk of infections, cardiovascular disease, diabetes, and osteoporosis among patients taking medium or high corticosteroid doses compared with those not on corticosteroids, but not among those taking low doses.

The risk of diabetes was 32% higher with medium corticosteroid doses and 76% higher with high doses, and the risk of osteoporosis was increased by 33% with medium doses and by 69% with high doses. The risk of cardiovascular diseases was 19% higher with medium doses and 31% higher with high doses.

For glaucoma, the risk was significantly increased, by 81%, in the high-dose group alone, while for depression, the risk was significantly higher, by 22%, only among those receiving medium doses.

“Although corticosteroids are inexpensive and readily accessible, their chronic use appears to have a significant long-term detrimental impact on health in patients with MG,” the team wrote. “These observations suggest that while the presence of MG increases the risk of key comorbid conditions, in most cases, treatment with corticosteroids may drive comorbidity development to a greater extent than MG itself.”

The scientists noted that most participants were older men, which may limit the generalizability of the findings to larger, more diverse populations.

Still, they said, the results highlight the importance for healthcare providers “to monitor and identify comorbidities early among MG patients receiving corticosteroid therapy, in order to provide prompt and appropriate management of adverse effects.”