MG-specific treatments needed for older patients, researchers say

A study of myasthenia gravis (MG) patients lends support to “ongoing efforts to develop efficacious MG-specific treatments with minimal short- and long-term adverse effects,” researchers said.

The U.S.-based study found that MG patients aged 65 and older have higher rates of death than those without the disease, mainly due to MG-related causes and a high burden of coexistent health conditions (comorbidities). Some 16% of the deaths among older MG patients during the study period were attributed to MG, which is consistent with what was observed in previous studies.

The study, “Survival Outcomes of Medicare-Covered Elderly US Population With Myasthenia Gravis,” was published in Muscle & Nerve.

MG is an autoimmune disease caused by self-reactive antibodies that attack proteins involved in the communication between nerve and muscle cells, leading to MG symptoms like muscle weakness and fatigue.

While the development of MG treatments and advanced respiratory support have helped to lower mortality among people with MG, there have been inconsistent results in terms of whether mortality among patients is comparable to that of those without the disease. “Additionally, long-term survival outcomes and causes of death have been inadequately studied among elderly MG patients in the United States (US),” the researchers wrote.

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Retrospective analysis

The researchers retrospectively analyzed 2006-2019 claims data from Medicare, the U.S. federal health insurance program for people aged 65 and older, as well as those with disabilities and specific conditions.

The final analysis included 6,024 people aged 65 and older identified as new MG cases and, for controls, 30,083 people without MG matched for age, sex, and other factors.

In both groups, most of the beneficiaries were men (54.8%) and non-Hispanic white (91.3%). Those aged 80 and older comprised the largest age group (36.4%).

The MG group experienced a shorter time to reach a 25% mortality rate than the control group (median of 4.5 years vs. a little over 5 years). The risk of death over the 10-year follow-up was 11% higher in men and 28% higher in women with MG than in those without MG.

In the control group, survival was significantly longer in women than in men.

The higher mortality among women with MG may be due to “a higher disease burden and more functional impairment, longer diagnostic delay, less tolerance to medications such as corticosteroids, and disparities in care,” the researchers wrote.

Some 36% of MG patients and 31.3% of controls died during the follow-up period, corresponding to average mortality rates per year of 5.1% and 4.5%, respectively. The mortality rate was higher among people with MG than in controls: 66.8 versus 57.1 per 1,000 person-years. Person-years represent the total number of patients and the total time each patient spent in the study.

Comorbidities that were more frequent among MG patients than controls included cardiovascular, metabolic, autoimmune, and infectious diseases. Statistical analyses showed that the Charlson Comorbidity Index (CCI) was significantly associated with survival, “while MG versus control was not statistically significantly associated with survival,” the team wrote.

The CCI is a weighted score used to assess a person’s comorbidities and predict their risk of death over 10 years.

“The results indicate that increased mortality among the MG group is explained by evolving comorbidities over time, rather than the MG diagnosis itself,” the team wrote.

The risk of death was higher in the four years after MG diagnosis, which is “consistent with prior observations that the disease is most difficult to control in its early period in the majority of patients,” the researchers wrote.

The most common cause of death in both groups involved cardiovascular disorders. Among the MG group, the second leading cause of death was MG-related complications, reported in 16% of the patients, or 11 per 1,000 person-years.

The mortality rate due to infections was higher in the MG group, and lower for cancer and dementia-associated mortality.

The researchers said this result is similar to what was observed in a European study, in which 15% of deaths in people with MG were related to the disease. Overall, the study demonstrates that “long-term mortality is increased in elderly MG patients compared to non-MG counterparts, driven by MG-related deaths and their greater comorbidities,” they wrote.