MG and its symptoms seen as harder on women, seronegative patients

Survey of 273 patients in Australia finds gender, antibody status differences

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Among people with myasthenia gravis (MG) living in Australia, women and seronegative patients — those whose tests fail to show MG-associated antibodies — reported a significantly higher disease toll in an online survey.

This toll included a greater range of disease symptoms, earlier disease onset, longer waits for an MG diagnosis, more exacerbations (episodes of disease worsening) and treatment side effects, and a poorer quality of life.

According to the researchers, survey findings support the need for “further research on gender and antibody status differentials regarding clinical features.”

Findings were detailed in the study “Clinical features, treatments, their impact, and quality of life for Myasthenia Gravis patients in Australia,” published in the Journal of Clinical Neuroscience.

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MG symptoms, overall burden higher in seronegative patients, mostly women

Marked by muscle weakness and fatigue, myasthenia gravis is due to the production of certain self-reactive antibodies that impair the communication between nerve and muscle cells. A common way of diagnosing the disease is by looking for these antibodies in the blood.

Disease prevalence in Australia is estimated — by a study that evaluated the prescriptions of pyridostigmine— to be 117 patients in every 1 million habitants. Pyridostigmine, an oral medicine sold under the brand name Mestinon, with generics available, often is recommended as a first-line treatment for MG.

“However, prevalence and incidence may be underestimated as not all MG patients are prescribed pyridostigmine,” the researchers wrote.

A previous community-based survey to assess the clinical features of MG patients in Australia was conducted in 2011.

A team led by researchers at the Australian National University ran an online survey from October 2021 to Jan. 28, 2022, to provide up-to-date perspectives into the experiences of MG patients in the country.

In total, 273 MG patients — 184 women and 89 men, with a mean age 60.5 — completed the survey.

Women had a longer disease duration than men, a mean of 12 vs. 8.4 years, and they were diagnosed at a significantly younger age, a mean of 45 vs. 61 years, results showed. However, women took longer to be diagnosed after symptom onset — an average of 3.5 years — than did men, whose average diagnosis came 1.5 years after symptoms started.

The most commonly reported symptoms included eye muscle weakness (92.9%); speech, chewing, and swallowing difficulties (82.1%); and muscle weakness in the neck, arms, and legs (79.3%).

In 43.2% of the patients, symptoms affected two-to-three regions of the body, but women had significantly more regions affected than men.

About one-fifth of patients reported being seronegative for myasthenia gravis

Blood tests for self-reactive antibodies were the most common method of diagnosis (65.8%), followed by a repetitive nerve stimulation test (47.5%), and a single fiber electromyography test (32%). These two tests assess the health of muscles and the nerve cells that control them.

More than half of the patients (56.8%) underwent more than one diagnostic test.

Most patients reported testing positive for antibodies targeting the acetylcholine receptor (55.9%), which is the leading cause of MG, and 7.9% reported being positive for antibodies targeting the MuSK protein, also involved in nerve-muscle communication.

About a fifth of the patients (22.2%) reported being seronegative; that is, they have no known MG-causing antibodies. Significantly more women (29%) than men (14%) reported having a seronegative status, the researchers noted.

People who were seronegative waited significantly longer for a diagnosis than did those who were seropositive (a mean of 5.3 vs. 2 years), and they started experiencing MG symptoms earlier in life, at a mean of 41.1 vs. 49.3 years old.

Disease exacerbations over the previous year also were more likely in seronegative patients, and these people required additional treatments across that year. Previous year crises were more common in women (37%) than men (23%).

About a third of all patients (32.4%) reported having at least one exacerbation in the year preceding the survey, with 44.4% of them being hospitalized.

Over the course of the disease, most patients were treated with an anticholinesterase, medications such as Mestinon (90.7%), oral corticosteroids (82.8%), immunosuppressive medications (69.2%), and intravenous immunoglobulin (IVIG) (62.4%). Plasmapheresis, or plasma exchange, was used sparingly (21.9%). Most patients (85%) were on a combination of different treatments.

“Only 33.6% patients reported undergoing a thymectomy,” the researchers noted. Those who underwent this surgical procedure to remove the thymus gland, considered a main disease treatment, reported a better quality of life.

Fatigue a common treatment side effect, reported by 86% of patients

Fatigue as a treatment side effect was reported by most patients (86%). Other frequent side effects, those reported by more than 57% of patients, included weight gain, difficulties in fighting off infections, gastrointestinal symptoms, and muscle weakness. The severity of these effects was significantly higher in female and seronegative patients, as measured by total mean scores on the Treatment Side-Effects Severity Scale.

MG also limited patients’ ability to engage in daily activities and took a toll on their life quality. In general, seronegative patients reported more quality of life limitations than seropositive patients.

“For women, MG is significantly associated with an earlier onset, longer disease duration, greater symptom load, having an exacerbation in the past year, greater severity, and impact from side-effects of treatment, a poorer QOL [quality of life] and greater out-of-pocket expenses for additional treatments, indicative of greater burden,” the researchers wrote.

“The survey identified areas for potential practice improvement in MG treatments … particularly for exacerbation management, and review with respect to current guidelines is recommended. Further research on gender and antibody status, to examine the differentials identified, is required,” they concluded.