Increased autoimmune disease burden before multiple sclerosis and neuromyelitis optica spectrum disorder diagnosis: A nationwide Korean cohort study

Background: A prodromal phase is increasingly recognized in multiple sclerosis and neuromyelitis optica spectrum disorder, but the temporal patterns of autoimmune diseases remain poorly characterized. Objectives: To evaluate the risk and timing of autoimmune diseases before multiple sclerosis and neuromyelitis optica spectrum disorder diagnosis. Methods: Using the Korean National Health Insurance Service database (2011–2021), we identified incident multiple sclerosis ( n = 3079) and neuromyelitis optica spectrum disorder ( n = 1407) cases, each matched with 10 controls by age, sex, and index year. Autoimmune diseases were assessed during the 10 years preceding the index year and categorized into early (5–10 years), intermediate (2–5 years), and late (0–2 years). Adjusted rate ratios were estimated using Poisson regression. Results: Autoimmune diseases occurred more frequently before the index year in multiple sclerosis (adjusted rate ratio = 1.58, 95% confidence interval = 1.46–1.71) and neuromyelitis optica spectrum disorder (adjusted rate ratio = 1.28, 95% confidence interval = 1.14–1.45) than controls, with the greatest differences in the late period. The adjusted rate ratio of autoimmune diseases in multiple sclerosis persisted across all periods, whereas the adjusted rate ratio was increased only in the intermediate and late periods in neuromyelitis optica spectrum disorder. Systemic autoimmune diseases, including systemic lupus erythematosus, Sjögren’s syndrome, and rheumatoid arthritis, were more frequent in both conditions. Conclusions: The burden of autoimmune disease is increased before multiple sclerosis and neuromyelitis optica spectrum disorder diagnosis.