1. Tumor necrosis factor inhibitor exposure in patients with autoimmune disease, particularly rheumatoid arthritis, was associated with increased risk of inflammatory central nervous system events.
Evidence Rating Level: 2 (Good)
The U.S. Food and Drug Administration has approved five tumor necrosis factor (TNF) inhibitors as immunotherapies for autoimmune diseases: etanercept, adalimumab, infliximab, golimumab, and certolizumab pegol. However, TNF inhibitor exposure has since been found to potentially be associated with inflammatory, demyelinating events in the central nervous system (CNS) including but not limited to multiple sclerosis and optic neuritis. This nested case-control study investigated TNF inhibitors (type, cumulative exposure duration, time of exposure) and subsequent risk of demyelinating (n = 56) and nondemyelinating CNS events (n = 50) in individuals with autoimmune disease. Participants with autoimmune disease were selected via the Mayo Clinic electronic medical record system across three sites. Between 2003 and 2019. The control group (no CNS events) was selected from the same system and matched 1:1 for sex, birth year, and autoimmune disease (n = 106). Participants were excluded if any inflammatory CNS events occurred prior to the development of an autoimmune disease. Thus, a total of 212 participants were included in this study (median [IQR] age at disease onset = 52 [43-62] years, 64% female). A total of 48 participants with inflammatory demyelinating CNS events had multiple sclerosis, optic neuritis, transverse myelitis, or neuromyelitis optica spectrum disorder (NMOSD). Common demyelinating CNS events were meningitis, idiopathic leptomeningitis, idiopathic pachymeningitis, idiopathic meningoencephalitis, autoimmune encephalitis, neurosarcoidosis, and CNS vasculitis. The experimental group was more likely to experience TNF inhibitor exposure (difference 20%), suggesting an association with increased risk of inflammatory CNS events (adjusted OR 3.01, 95% CI 1.55 to 5.82, p = 0.001). Upon stratification by nondemyelinating and demyelinating events, results remained similar. Further analyses suggested a primary association among those with rheumatoid arthritis (adjusted OR 4.82, 95% CI 1.62 to 14.36, p = 0.005). Overall, this study supports the hypothesis that TNF exposure is associated with increased odds of inflammatory CNS events in individuals with autoimmune disease. Further research is warranted to determine when this increased risk is introduced and how to improve these outcomes.
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