Effect of TNF-α blockers on reducing the risk of dementia in rheumatoid arthritis: a nationwide cohort study

Objective Rheumatoid arthritis (RA) and Alzheimer’s disease (AD) share characteristics of chronic inflammation and immune system dysregulation. RA patients are known to have an increased risk of dementia, yet studies on the association between tumour necrosis factor (TNF)-α blocker use and dementia risk in RA patients are lacking. This population-based cohort study aimed to investigate whether TNF-α blocker use is associated with a reduced risk of dementia in RA patients. Methods Using Taiwan’s National Health Insurance Research Database, we identified RA patients treated with TNF-α blockers (etanercept, adalimumab and golimumab) and matched them 1:4 with RA patients receiving conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). A stratified Cox proportional hazard model was used to compare dementia risk between these groups. Results Among 3.987 RA patients using TNF-α blockers and 20,689 RA patients not using TNF-α blockers (comparison group), no significant difference in dementia risk was initially observed. However, upon further analysis stratified by TNF-α blocker exposure, RA patients with long-term (>180 cumulative defined daily dose [cDDD]) TNF-α blocker use had a significantly lower risk of dementia (adjusted hazard ratio [aHR]=0.578, 95% confidence interval [CI]=0.342-0.977), after adjusting for age, sex and comorbidities. Moreover, higher cumulative doses (>1036 cDDD) of TNF-α blockers were associated with a further reduced risk of dementia (aHR=0.387, 95% CI=0.188-0.793). Conclusion This nationwide cohort study suggests that long-term and higher cumulative doses of TNF-α blockers may be associated with a lower risk of dementia in patients with RA.