Risk Factors for MG Exacerbations, Myasthenic Crises ID’d in Study
Disease severity at diagnosis and levels of self-reactive antibodies are independent risk factors for myasthenic crisis and disease exacerbations, a German study suggests.
Close monitoring, particularly of infections, is important to prevent disease worsening in people with myasthenia gravis (MG), the researchers noted.
MG is caused by self-reactive antibodies that mistakenly attack proteins involved in nerve-muscle communication, causing patients to experience muscle weakness, including in the muscles that control breathing. In most cases, MG-causing antibodies specifically target a protein called acetylcholine receptor, but more rarely, antibodies targeting another protein called muscle-specific kinase (MuSK) cause MG.
Worsening episodes, which include both myasthenic crisis (MC) and disease exacerbations, are known to contribute to the disease burden in patients who fail to respond properly to therapies. However, the factors that heighten these worsening events are still poorly described.
To identify potential risk factors of MC and exacerbations, a team led by researchers at the Heinrich Heine University Düsseldorf analyzed MG patients diagnosed between 2000 and 2021 at eight university hospitals in Germany.
For their analysis they defined a MC as “a rapid clinical decline requiring non-invasive ventilation, intubation or parenteral nutrition” along with severe difficulty in swallowing that required a feeding tube.
Disease exacerbation was defined according to the quantitative myasthenia gravis score (QMG) and following national guidelines. An exacerbation was defined by a QMG score of at least 8 points and a minimum increase of 5 points from a patient’s last follow-up. Ocular findings did not account for more than 5 points on the QMG score. Additional criteria included progressive clinical muscle or breathing function deterioration, with symptoms progressing for no more than 30 days.
Whenever a patient showed symptoms of both MC and exacerbations, they were classified as MC.
In total, they analyzed 815 patients (mean age at diagnosis, 53.5 years), of whom 300 (36.8%) had early disease onset (before their 50s). Patients were followed for a mean of 62.6 months (around five years). Most had generalized MG (72.7%), while the remaining 26.3% had ocular MG.
Overall, 217 patients (26.3%) experienced a MC and 225 (27.6%) a disease exacerbation.
Statistical analyses identified disease severity at diagnosis, the presence of a thymoma (a tumor in the thymus gland), and anti-MuSK antibodies as predictors for MC or disease exacerbation occurrence. Generalized disease was also identified as an independent risk factor for exacerbation.
Patients who achieved minimal manifestation status 12 months after diagnosis — defined as no functional limitation and weakness detected only by examination — had a lower risk of MC and disease exacerbation than those without.
The time since diagnosis and the start of immunosuppressive therapy did not affect the risk.
Researchers also assessed which factors could be associated with a worse outcome after a MC. This analysis included 229 patients who had a crisis and survived.
Patients with worse outcomes following MC were older, had a higher score in the Myasthenia Gravis Foundation of America (MGFA) class, and a lower vital capacity before and at admission. The MGFA score is a quantitative measure of disease severity for people with MG. Vital capacity is a lung function parameter that indicates the total amount of air exhaled after a deep breath.
The number of additional health conditions at admission, the need for intubation and prolonged mechanical ventilation, as well as MC triggered by infections were also seen as factors contributing to a worse outcome.
No differences were seen with different treatments regimens, specifically between into-the-vein immunoglobulins versus plasma exchange or both combined.
“MC and disease exacerbations inflict a substantial burden of disease on MG patients,” the researchers wrote. “Disease severity at diagnosis and antibody status predicted the occurrence of MC and disease exacerbation.”
“Intensified monitoring with emphasis on the prevention of infectious complications could be of value to prevent uncontrolled disease in MG patients,” they wrote.