Potential long-term effect of tumor necrosis factor inhibitors on dementia risk: A propensity score matched retrospective cohort study in US veterans

Abstract

Introduction: Tumor necrosis factor (TNF) inhibitors are widely used to treat rheumatoid arthritis (RA) and their potential to retard Alzheimer's disease (AD) progression has been reported. However, their long-term effects on the dementia/AD risk remain unknown.

Methods: A propensity scored matched retrospective cohort study was conducted among 40,207 patients with RA within the US Veterans Affairs health-care system from 2000 to 2020.

Results: A total of 2510 patients with RA prescribed TNF inhibitors were 1:2 matched to control patients. TNF inhibitor use was associated with reduced dementia risk (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.52-0.80), which was consistent as the study period increased from 5 to 20 years after RA diagnosis. TNF inhibitor use also showed a long-term effect in reducing the risk of AD (HR: 0.57, 95% CI: 0.39-0.83) during the 20 years of follow-up.

Conclusion: TNF inhibitor use is associated with lower long-term risk of dementia/AD among US veterans with RA.

Keywords: Alzheimer's disease; US veterans; cohort study; dementia; long-term effect; rheumatoid arthritis; tumor necrosis factor inhibitor.

Conflict of interest statement

Conflict of Interest Disclosures

None of the authors have financial interests to disclose.

© 2021 the Alzheimer's Association.

Figures

Figure 1

Forest plot shows the association of TNF inhibitor use with overall dementia risk in patients with RA using Cox proportional hazards regression. Note: For individual TNF inhibitor, control group was patients without TNF inhibitor use; For TNF inhibitor combination use group, control group was patients with one of TNF inhibitors.

Figure 2

Forest plots of dementia risk in TNF inhibitor-treated patients with RA with different lengths of study periods, compared to those without TNF inhibitor treatment. (A) Dementia risk over five years of study period. (B) Dementia risk over 10 years of study period. (C) Dementia risk over 15 years of study period. (D) Dementia risk over 20 years of study period. Note: Multivariate-adjusted Cox proportional hazards regression was used in the analysis.

Figure 3

Forest plots of dementia risk in TNF inhibitor-treated patients with RA older than 65 years old, compared to those without TNF inhibitor treatment. (A) Overall dementia risk during the entire study period. (B) Dementia risk over five years of study period. (C) Dementia risk over ten years of study period. (D) Dementia risk over 15 years of study period. Note: Multivariate-adjusted Cox proportional hazards regression was used in the analysis.

Figure 4

Forest plots of AD risk in TNF inhibitor-treated patients with RA, compared to those without TNF inhibitor treatment. (A) Overall AD risk in adult RA patients during the entire study period. (B) Overall AD risk in RA patients older than 65 years during the entire study period. Note: Multivariate-adjusted Cox proportional hazards regression was used in the analysis.