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

1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14

 

  1. Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
  2. Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei; and Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  3. Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei; and Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
  4. Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, and Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  5. Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
  6. Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
  7. Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
  8. Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Camillian Saint Mary's Hospital, Luodong, Yilan County, Taiwan.
  9. Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, and Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Cardinal Tien Hospital, Yonghe Branch, New Taipei City, Taiwan.
  10. Health Data Analytics and Statistics Center, Office of Data Science, Taipei Medical University, Taipei, Taiwan.
  11. Department of Mathematics and Statistics, Idaho State University, Pocatello, ID, USA.
  12. Health Data Analytics and Statistics Center, Office of Data Science, Taipei Medical University, Taipei, and Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan.
  13. Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
  14. Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei; and Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. ccchang@tmu.edu.tw

CER18015
2025 Vol.43, N°5
PI 0931, PF 0938
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PMID: 40095620 [PubMed]

Received: 26/07/2024
Accepted : 06/02/2025
In Press: 13/03/2025
Published: 08/05/2025

Abstract

OBJECTIVES:
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).
CONCLUSIONS:
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.

DOI: https://doi.org/10.55563/clinexprheumatol/6oto0h

Rheumatology Article