Increase in Late-Onset MG Has Implications on Prognosis, Adverse Events

Prognostic implications have come into play with the changing epidemiology of myasthenia gravis (MG), as the increased rate of very-late-onset MG (VLOMG) has affected prognoses in patients due to adverse events and long-term treatment exposure. According to a new study published in the Journal of Neurology,¹ those with VLOMG very rarely saw remission compared with early-onset MG (EOMG).

The incidence of MG has increased in patients over time, although the exact cause is unknown. The majority of patients with MG (80%-85%) have autoantibodies to acetylcholine receptors (AChR-Abs),² and 5% to 6% have autoantibodies to muscle-specific tyrosine kinase (MuSK); 10% to 15% have no detectable autoantibodies. Response to treatment, immunopathogenesis, and demographics are all different based on these groups and have effects on the approach to the condition. This study aimed to assess how the demographics of MG have changed over time and how the changes in demographics, including sex, age at onset, treatment-related adverse events, and disease severity, can affect long-term prognosis when using therapy.

The study enrolled patients with AChR-MG who had an age of onset of 18 years or older and were treated between January 1, 1970, and October 31, 2020, at a tertiary MG center in Rome. All patients were followed for 2 or more years by October 2022. The population included all of the AChR-Ab–positive patients, double-seronegative patients, and MuSK-Ab–positive patients. Patients with AChR-Ab MG were separated into groups of EOMG with disease onset between 18 and 49 years of age, LOMG with onset between 50 and 64 years of age, and VLOMG with onset at 65 years or older.

Medical records were used to extract data, including demographics of age of onset, sex, decade of onset, severity of MG, and clinical pattern. Treatment efficacy and tolerance were assessed in patients who had an onset of disease between January 1, 2000, and October 31, 2020, and who had follow-up data for at least 2 years. Possible differences in long-term outcomes were assessed at the last follow-up. Treatment-related adverse events were reported.

There were 1215 patients included in the study, where the frequency of AChR-positive patients increased with age of onset, and the association was significant in a multivariable logistic regression (OR, 1.02 per 1-year increase in age of disease onset; 95% CI, 1.01-1.03) and remained significant after adjusting for ocular MG, thymoma, and sex.

There were 1023 patients with AChR-MG, and the median (IQR) age of onset was 52 years (34-66); 51% were women. EOMG was found in 30.9% of the patients, 14.9% had LOMG, and 24.8% had VLOMG. Also, VLOMG increased in frequency from 5% in the 1970-1979 decade to 45% in the 2010-2020 decade, with EOMG decreasing in that same time span. Women made up 76% of the EOMG group vs 26% of the LOMG and 33% of the VLOMG groups.

There were 517 cases of MG that were included in the treatment outcome analysis. A total of 88.4% of the patients required an immunosuppressant at some point during the disease. Minimal manifestation or better was found in 68% of patients with EOMG, 60% of patients with LOMG, and 60% of patients with VLOMG at the end of the follow-up, the rate of minimal manifestation or better with a dose of prednisone of 5 mg or less was 60% in EOMG, 44% in LOMG, and 48% in VLOMG. Complete stable remission was highest in EMOG compared with LOMG and VLOMG (24% vs 11% and 4%, respectively).

Patients with onset between 2000 and 2009 were more likely to achieve minimal manifestation or better with a dose of 5 mg or less of prednisone compared with those with onset in the past decade (51% vs 42%), and complete remission was also higher in those with onset between 2000 and 2009 compared with those in the following decade (17% vs 3%). Higher odds of moderate to severe disease (OR, 2.07; 95% CI, 1.32-3.25) and lower odds of achieving complete remission (OR, 0.17; 95% CI, 0.06-0.43) were found in women in the study. Women were also less likely to be treated with corticosteroids plus 2 or more immunosuppressants (OR, 0.40; 95% CI, 0.16-0.96).

There were some limitations to this study. The study took place in a single center and had a cross-sectional and retrospective design, which could have influenced the results. The high rates of difficult-to-treat and thymoma cases could have been due to the single tertiary referral center being the site of the study.

The authors concluded that further studies would need to be conducted to assess the safety profile of therapies and to improve management of MG. “Our study provides novel insights that could be useful to optimize treatment and address current and future challenges of MG management,” the authors wrote. “Looking ahead, epidemiological changes are likely to influence the overall MG prognosis in the coming years…. As elderly MG patients have the highest risk of [adverse events], careful surveillance and active prevention are crucial to clinical management.”

References

1. Falso S, Spagni G, Monte G, et al. Half a century of change: demographic trends and their clinical impact in acetylcholine receptor antibody-positive myasthenia gravis. J Neurol. 2026;273(4):227. doi:10.1007/s00415-026-13670-y
2. Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren JJGM. Myasthenia gravis. Nat Rev Dis Primers. 2019;5(1):30. doi:10.1038/s41572-019-00