Half a century of change: demographic trends and their clinical impact in acetylcholine receptor antibody-positive myasthenia gravis

Background: The impact of myasthenia gravis (MG) changing epidemiology on disease management remains unclear. We investigated how MG subtypes changing over the last 50 years have affected disease prognosis. Methods: Adult patients with MG onset between 1970 and 2020, followed up at our center for ≥ 2 years, were included in this retrospective study. Demographics, MG subtypes, and antibody (Ab) status over the last 50 years were assessed. Treatment response and adverse events (AEs) were evaluated in acetylcholine receptor (AChR)-MG patients with onset between 2000 and 2020. Treatment goal was defined as Post-Intervention Status of “minimal manifestations” or better with corticosteroid dose ≤ 5 mg/day (5 mg-MM-or-better). Results: We included 1023 AChR-MG patients, of whom 517 had onset between 2000 and 2020. In the non-thymoma population, the median age at onset increased from 35 years in the 1970 s to 65 in the last decade (p < 0.0001), and the AChR-Ab positivity rate correlated with age at onset (p = 0.0002). Early-onset MG (EOMG) had the highest rate of 5 mg-MM-or-better (62/104, 60%), followed by very late-onset MG (VLOMG, 91/192, 48%; p = 0.0012). Complete stable remission (CSR) was rare in VLOMG (8/192, 4%) and most frequently occurred in EOMG (25/104, 24%; p < 0.0001). At multivariable logistic regression 5 mg-MM-or-better was associated with EOMG, VLOMG, and follow-up duration, while negatively associated with moderate-to-severe MG and treatment-related AEs. VLOMG and late-onset MG, along with the use of steroids plus one or ≥ 2 immunosuppressants, were independent risk factors for AEs. Discussion: The increased rate of VLOMG has relevant therapeutic and prognostic implications, mainly related to long-term treatment exposure and high risk of AEs in elderly patients.