Neuroinflammation Associated with TNF-alpha Inhibitor Exposure

Objective: To identify the frequency and clinical spectrum of neuroinflammation associated with exposure to tumor necrosis factor alpha inhibitors (TNFi). Methods: We performed a single-system retrospective cohort study. Adults in the Yale New Haven Health System with documented use of any FDA-approved TNFi between 2007-2017 were identified via automated review of the electronic medical record. Those who also had brain MRIs were identified and categorized as either TNFi exposed or unexposed. Individuals with MRI findings concerning for neuroinflammation were identified and detailed chart reviews were performed. Results: A total of 4391 patients received TNFi and 547 also had brain MRI. After exclusion criteria were applied, 375 MRIs occurred after TNFi exposure and 132 MRIs occurred prior to TNFi. MRIs were normal for 20.8% of exposed patients. The most common abnormal finding was nonspecific, punctate T2 hyperintensities. Seventeen cases (4.5%) among the exposed cohort had findings consistent with neuroinflammation, of which 58.8% required TNFi discontinuation and additional immunotherapy while an additional 23.5% discontinued TNFi alone. After 3 years, 70.6% had stable MRI findings while 11.8% demonstrated progression. 10-year period prevalence of neuroinflammation in all subjects exposed to TNFi was 0.4%. Conclusions: Neuroinflammatory phenomena following TNFi is a common concern for those treating patients with autoimmune disease. This is a large-scale study identifying the epidemiology surrounding this phenomenon. TNFi-associated inflammation was a rare outcome in our cohort. Most treated patients had either normal or nonspecific MRI findings. Further risk stratification parameters need to be identified.