Cited by 196Rheumatoid Arthritis Research and TherapiesDementia and Cognitive Impairment ResearchAlzheimer's disease research and treatments

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Treatment for Rheumatoid Arthritis and Risk of Alzheimer’s Disease: A Nested Case-Control Analysis

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Chou, Richard C., Kane, Michael, Ghimire, Sanjay, Gautam, Shiva, Gui, Jiang·2016·CNS Drugs

DOI 10.1007/s40263-016-0374-zPMC PMC5585782

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Abstract

Introduction It is increasingly becoming accepted that inflammation may play an important role in the pathogenesis of Alzheimer's disease (AD), as several immune-related genes have been associated with AD. Among these is tumor necrosis factor (TNF)-α, a proinflammatory cytokine known to play an important role in autoimmune disorders, including rheumatoid arthritis (RA). Although AD and RA appear to involve similar pathological mechanisms through the production of TNF-α, the relationship between AD and RA remains unknown.Objective To determine the relative risk of AD among RA patients and non-RA patients, and whether anti-TNF therapy for RA was associated with a lower risk of AD in RA patients.Methods We performed a nested case-control study of more than 8.5 million commercially insured adults (aged ≥18 years) in all 50 US states, Puerto Rico, and US Virgin Islands in the Verisk Health claims database. We derived a sub-cohort of subjects with a diagnosis of RA (controls), or RA and AD (cases), matching cases and controls based on age, sex, exposure assessment period, and methotrexate treatment. We also assessed relative risk of AD following exposure to standard RA therapies, including anti-TNF agents (infliximab, adalimumab, etanercept), methotrexate, prednisone, sulfasalazine, and rituximab. Odds ratios were adjusted for comorbidities, including coronary artery disease, diabetes mellitus, and peripheral vascular disease.Results AD was more prevalent (p < 0.0001) among RA patients (0.79 %) than among those without RA (0.11 %). Chronic conditions such as coronary artery disease (odds ratio [OR] 1.48; 95 % confidence interval [CI] 1.04-2.05; p = 0.03), diabetes (OR 1.86; 95 % CI 1.32-2.62; p = 0.0004), and peripheral vascular disease (OR 1.61; 95 % CI 1.06-2.43; p = 0.02) significantly increased the relative risk of AD among RA patients. Exposure to anti-TNF agents as a class, but not other immunosuppressive drugs studied, was associated with lowered risk of AD among RA patients (unadjusted OR 0.44; 95 % CI 0.22-0.87; p = 0.02; adjusted OR 0.45; 95 % CI 0.23-0.90; p = 0.02). Sub-group analysis demonstrated that of the three anti-TNF agents studied, only etanercept (unadjusted OR, 0.33; 95 % CI 0.08-0.94; p = 0.03; adjusted OR 0.30; 95 % CI 0.08-0.89; p = 0.02) was associated with a decreased risk of AD in RA patients.Conclusion There is an increased risk of AD in the studied RA population. The relative risk of AD among RA subjects was lowered in those exposed to etanercept. Anti-TNF therapy with etanercept shows promise as a potential treatment for AD.

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Authors: Chou, R. C., Kane, M., Ghimire, S., Gautam, S., & Gui, J.
Affiliations: Dartmouth College (US)
Harvard University (US)
Beth Israel Deaconess Medical Center (US)
Corresponding author: Chou, Richard C.
ORCID: Gui, Jiang
Venue: CNS Drugs
Publisher: Springer Science and Business Media LLC
Published: 2016-07-28
Volume: 30
Issue: 11
Pages: 1111-1120
ISSN: 1172-7047 (ISSN-L)
1179-1934
DOI: 10.1007/s40263-016-0374-z
PMC: PMC5585782
OpenAlex: W2489613804
Cited by: 194
References: 53
Citations by year: 2026: 14 · 2025: 14 · 2024: 17 · 2023: 24 · 2022: 33 · 2021: 27 · 2020: 23 · 2019: 21 · 2018: 12 · 2017: 6 · 2016: 1
FWCI: 14.19
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (unspecified)
Locations: CNS Drugs (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (P30CA023108)
U.S. National Library of Medicine (R01LM012012)
National Center for Research Resources (UL1RR025758)
Topics: Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: rheumatoid arthritis, Alzheimer's disease, anti-TNF therapy, TNF-α, inflammation, methotrexate, infliximab, adalimumab, etanercept, rituximab, sulfasalazine, prednisone, comorbidities, coronary artery disease, diabetes mellitus, peripheral vascular disease, immunosuppressants
MeSH terms: Adult, Aged, Alzheimer Disease, Arthritis, Rheumatoid, Female, Humans, Male, Middle Aged, Risk, Tumor Necrosis Factor-alpha, Cohort Studies, Case-Control Studies, Antirheumatic Agents

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Treatment for Rheumatoid Arthritis and Risk of Alzheimer’s Disease: A Nested Case-Control Analysis

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