Most patients with late-onset myasthenia gravis (LOMG) — those whose disease appears at age 50 or later and is not related to tumors in the thymus gland — are men, have mild-to-moderate disease, and respond well to treatment with oral prednisone combined with azathioprine, a study in Turkey reports.
The study, titled “Late-onset generalized myasthenia gravis: clinical features, treatment, and outcome,” was published in the journal Acta Neurologica Belgica.
Myasthenia gravis (MG) is a neuromuscular disorder characterized by muscle weakness and muscle fatigue. This autoimmune disease occurs when antibodies inappropriately attack and destroy certain receptors — ones important for muscle contractions — that are found on the surface of muscle cells, breaking down nerve transmission to muscles.
In most patients, these autoantibodies are directed against acetylcholine receptors (AChR), and known as anti-AChR. Less frequently, patients have autoantibodies against MuSK (Muscle-Specific Kinase), a protein related to acetylcholine receptors.
The disorder usually emerges during adulthood, although symptom onset may occur at any age. In some people, the disease appears at older ages, in which case it is referred to as late-onset myasthenia gravis (LOMG).
A lot of clinical information has been gathered on LOMG, but few studies have looked into the severity and treatment outcomes of this specific form of the disease.
The inclusion of other types of MG in prior studies, including ocular MG and MG associated with thymomas — tumors of the thymus gland — has made it difficult to narrow down any findings only pertinent to LOMG.
To gather such specific information, researchers now analyzed 95 patients with generalized MG, without thymomas, whose disease appeared at age 50 or older.
All patients were followed for three to 12 years at an outpatient clinic in Istanbul, Turkey, and their clinical characteristics, severity of disease, and antibody test results were evaluated. In a subset of patients, responses to treatment also were analyzed.
Most people with late-onset MG were men (63%), and their first symptoms usually started in the eye (62% of patients), spreading over time to other muscles in the body.
Close to half of the patients (47%) had mild disease (maximum MGFA Class 2), with nearly all of the remainder presenting with moderate (35%) or severe (12%) disease. Those with moderate disease had a maximum MGFA Class 3, while those with severe disease had a maximum MGFA Class 4.
A smaller number of people with late-onset MG, 6%, had the severest stage of the disease, requiring mechanical ventilation (max. MGFA Class 5).
The majority of individuals tested positive for anti-AChR antibodies in their blood (80%), which were present at particularly high levels in older people in their 70’s and 80’s.
Anti-MuSK antibodies were detected in five patients. In contrast with the rest of the group, disease onset among anti-MuSK carriers started with bulbar rather than ocular symptoms, affecting the face and throat muscles. This included one person with head drop. In all except one, the disease was severe, but they responded favorably to treatment. “This suggests that MuSK MG may be easier to treat in older people,” the researchers said.
Many patients also carried antibodies targeting the protein titin (61%), which have been closely associated with older-onset MG in prior studies. Similarly to anti-AChR carriers, older patients also had elevated levels of anti-titin.
Half of them had mild disease, and 60% had favorable treatment outcomes, the study found. Thus, neither anti-titin nor anti-MuSK antibodies seemed to be associated with worse disease severity or prognosis.
Treatment responses were evaluated in 84 participants who had been given immunosuppressive therapy. Among them, 22 were given oral prednisone only, and 12 were given oral azathioprine only, with the remaining 50 patients receiving the two treatments combined.
At the end of follow-up, most patients — 60% at the end of three years and 63% at the last follow-up visit — were responding favorably to therapy.
Participants who responded positively to the treatment fell into three groups. Some were free of any signs or symptoms of the disease and had received no treatment for at least one year, which was identified as complete stable remission, or CSR. Others were free of disease manifestations but still under therapy, called pharmacological remission, or PR. The rest were experiencing minimal muscle weakness only — identified as minimal manifestations, or MM — that did not limit their daily life.
On further analysis, prednisone combined with azathioprine was found to be the only regimen with a significant benefit, as compared with the use of each agent alone, and the only prognostic factor with a positive effect on patients’ outcomes.
Low-dose prednisone (30 mg/day or less) plus azathioprine seemed to be sufficient to treat mild disease in older people, the study also found. “It is possible that older people respond better-to-low doses of immunosuppressives, compared to young people,” the researchers said.
“In conclusion, our study confirms previously known information on LOMG. It further supports within a specific MG population the benefit of adding AZA [azathioprine] to PRED [prednisone],” they concluded.