Antibiotic drug use in the five years preceding the diagnosis of multiple sclerosis

Background: Microbiota may play a role in autoimmune disease pathogenesis, including multiple sclerosis (MS). Antibiotic use disrupts the microbiome and may increase the risk of autoimmune diseases. We evaluated the relationship between MS diagnosis and antibiotic, antimycotic and antiviral drug use in the 5 years preceding diagnosis. Method: Our population-based case-control study used German ambulatory claims data from 2012 to 2022. We defined cohorts of 13,053 MS patients, 22,898 Crohn's disease patients, and 15,037 matched controls without autoimmune diseases, aged 21-70. Logistic and Poisson regression models explored the relationship between MS diagnosis and antimicrobial usage. Two sub-analyses were performed: a separate analysis of patients with clinically isolated syndrome (CIS) and a sensitivity analysis of newly diagnosed MS patients without preceding neurological symptoms. Results: Patients with MS had higher exposure to antibiotic (Odd Ratio (OR) = 1.27, 95 % CI 1.21-1.33), antimycotic (OR = 1.27, 95 % CI 1.12-1.45), and antiviral drugs (OR = 1.28, 95 % CI 1.15-1.43) in the five years before diagnosis compared to patients with no autoimmune diseases. Similar findings were obtained for the CIS cohort and in the sensitivity analysis. Antibiotic use peaked 5 years before MS diagnosis, declining closer to diagnosis, while antiviral and antimycotic drug use showed the opposite. This effect was not observed in the sensitivity analysis and CIS cohorts. Antibiotic use was higher in Crohn's disease than in MS (OR = 0.86, 95 % CI 0.82-0.90), with no consistent differences in antimycotic and antiviral use. Conclusions: The association and kinetic of antibiotic use before MS and CIS diagnosis supports the role of microbiota in MS pathogenesis and suggests antibiotic use to be related to the development of autoimmune diseases, including MS. Additional studies are warranted to clarify whether increased antibiotic use is part of the MS prodrome or a true risk factor for MS.