Myasthenia gravis (MG) tends to be more severe and generalized at diagnosis, and myasthenic crises more frequent in patients whose disease is associated with thymoma, an analysis of a patient registry has found.
MG patients with thymoma also required more immunosuppressive and immunomodulatory therapies, its scientists said. Identifying those in high-risk groups may help to guide treatment management.
Findings were reported in the study, “Clinical characteristics and outcomes of thymoma associated myasthenia gravis,” published in the European Journal of Neurology.
MG is an autoimmune disease characterized by weakness and fatigue, which can be localized to eye muscles or be more generalized, affecting many muscles, including those required for breathing. In most cases, MG is caused by self-reactive antibodies targeting acetylcholine receptors (AChRs) in the neuromuscular junction, the place where nerve endings contact and communicate with muscle fibers.
Rare tumors in the thymus gland, commonly known as thymomas, are found in up to 15% of MG patients. In turn, statistics indicate that 30–45% of people with a thymoma eventually go on to develop MG. Almost all MG patients with a thymoma also have anti-AChR antibodies.
However, associations between thymoma and MG severity, and between thymoma and response to treatment, are not clear, as studies have reported conflicting results.
While surgical removal of the thymus — a procedure known as thymectomy — is a standard treatment, it also is not yet established whether patients unable to undergo this surgery, or those who see their thymoma return after the procedure, have a worse MG prognosis.
To fill these knowledge gaps, researchers at the Autonomous University of Barcelona and colleagues extracted patient medical data from the nationwide MG registry, which is part of the Spanish Registry of Neuromuscular Diseases.
Those selected were 18 and older (adults), had at least one year of follow-up data, and were positive for anti-AChR antibodies.
The study included a total of 964 patients, of whom 148 (15.4%) had a thymoma and the remaining 816 (84.6%) did not. Although thymoma was equally frequent in both sexes, at onset, those with thymoma were younger than patients without (52 vs. 60.4 years old).
Generalized symptoms at onset were more frequent in those with a thymoma, and purely eye-related symptoms less frequent in this group. Bulbar onset (facial muscle weakness) was equally frequent in both patient groups.
All treatments were equally used regardless of thymoma status, except for the immunosuppressants CellCept (mycophenolate mofetil) and cyclosporine, as well as plasmapheresis (plasma exchange) or intravenous immunoglobulin infusions, which were used more frequently in the thymoma group.
Based on the Myasthenia Gravis Foundation of America (MGFA) clinical classification, participants with thymoma presented more severe clinical forms at onset and experienced more moments of severe disease. At follow-up, however, there were no differences in MGFA classification between the two groups.
Disease manifestations considered to be more than minimal by MGFA standards were more frequently seen in thymoma patients at one year, five years, and by the end of follow-up.
At least one myasthenic crisis — a rapid worsening of symptoms requiring ventilation — was experienced by 96 patients during follow-up. Of these, 29 had a thymoma, and 67 did not.
Myasthenic crises were more frequent in thymoma patients. The average time between thymus removal and the first myasthenic crisis in thymoma patients was just over three years.
Admission to a hospital’s intensive care unit was also more frequent in thymoma patients.
Moreover, 36.5% of thymoma patients failed to respond to treatment, while 19.7% of those without a thymoma showed lack of treatment response.
After adjusting for age at disease onset, investigators found that thymoma patients had a 2.46-times higher risk of mortality.
All, except two patients with a thymoma, underwent thymectomy. Further examination of thymoma tissue from 108 samples extracted to identify tumor subtypes found no differences between each thymoma subtype in the MGFA scale at the last follow-up, or in treatment responsiveness or mortality.
At least one recurrence of thymoma occurred in 27 (18.1%) patients, and 13 (48%) recurrences coincided with a worsening of symptoms.
People whose thymoma returned tended to have a worse MGFA prognosis, were more likely to not respond to treatment (become refractory), and were more likely to die than thymoma patients whose tumor did not return. Those whose thymoma could not be entirely removed also had a worse MG prognosis and higher mortality.
“In conclusion, our data suggest that patients with thymoma-associated MG have a worse prognosis,” the scientists wrote.
“As MG is a highly variable disease in which well-defined prognostic factors are lacking, identification of high-risk subgroups is capital to establish prognosis and guide individualized management,” they concluded.
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