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Treatment with TNF‐α inhibitors versus methotrexate and the association with dementia and Alzheimer's disease
INTRODUCTION: Peripheral inhibition of tumor necrosis factor (TNF)‐α, outside of the central nervous system, may result in clinical improvement of Alzheimer's disease (AD) outcomes. TNF‐α inhibitors (TNFIs) are effective treatments for various autoimmune conditions and may be effective for prev...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450793/ https://www.ncbi.nlm.nih.gov/pubmed/34584936 http://dx.doi.org/10.1002/trc2.12163 |
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author | Kern, David M. Lovestone, Simon Cepeda, M. Soledad |
author_facet | Kern, David M. Lovestone, Simon Cepeda, M. Soledad |
author_sort | Kern, David M. |
collection | PubMed |
description | INTRODUCTION: Peripheral inhibition of tumor necrosis factor (TNF)‐α, outside of the central nervous system, may result in clinical improvement of Alzheimer's disease (AD) outcomes. TNF‐α inhibitors (TNFIs) are effective treatments for various autoimmune conditions and may be effective for preventing and/or treating AD. The objective of this study was to compare the risk of dementia and AD in patients initiating methotrexate versus those initiating TNFIs. METHODS: Insurance claims data from databases of commercially insured and Medicare‐eligible patients were used to estimate the risk of dementia and AD within patients with rheumatoid arthritis (RA) initiating a TNFI versus initiation of methotrexate. A sensitivity analysis included all patients without the RA diagnosis requirement. The at‐risk period spanned from the index date until a diagnosis of the outcome, loss‐to‐follow‐up, or receipt of the comparator drug. Patients were matched 1‐to‐1 using propensity scores. A Cox proportional hazards model was used to estimate the hazard ratio (HR). Negative controls were used to calibrate the results. RESULTS: A total of 11,092 new TNFI patients and 44,023 new methotrexate patients were identified, and 8925 from each group were matched. The outcome of dementia occurred in 1.4% of patients in both groups. The calibrated results from the Cox regression found no difference between the two groups (commercially insured database: calibrated HR = 0.69, 95% confidence interval = 0.45 to 1.05; Medicare‐only database: 1.14, 0.66 to 1.96). Results were similar in all sensitivity analyses: outcome of AD and including patients without RA. DISCUSSION: No significant difference for the risk of dementia or AD was seen between patients initiating a TNFI versus methotrexate. Although this study cannot conclude whether use of TNFIs is protective against dementia and AD compared with receiving no treatment, there was no evidence that it is more protective than the active comparator methotrexate. |
format | Online Article Text |
id | pubmed-8450793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84507932021-09-27 Treatment with TNF‐α inhibitors versus methotrexate and the association with dementia and Alzheimer's disease Kern, David M. Lovestone, Simon Cepeda, M. Soledad Alzheimers Dement (N Y) Research Articles INTRODUCTION: Peripheral inhibition of tumor necrosis factor (TNF)‐α, outside of the central nervous system, may result in clinical improvement of Alzheimer's disease (AD) outcomes. TNF‐α inhibitors (TNFIs) are effective treatments for various autoimmune conditions and may be effective for preventing and/or treating AD. The objective of this study was to compare the risk of dementia and AD in patients initiating methotrexate versus those initiating TNFIs. METHODS: Insurance claims data from databases of commercially insured and Medicare‐eligible patients were used to estimate the risk of dementia and AD within patients with rheumatoid arthritis (RA) initiating a TNFI versus initiation of methotrexate. A sensitivity analysis included all patients without the RA diagnosis requirement. The at‐risk period spanned from the index date until a diagnosis of the outcome, loss‐to‐follow‐up, or receipt of the comparator drug. Patients were matched 1‐to‐1 using propensity scores. A Cox proportional hazards model was used to estimate the hazard ratio (HR). Negative controls were used to calibrate the results. RESULTS: A total of 11,092 new TNFI patients and 44,023 new methotrexate patients were identified, and 8925 from each group were matched. The outcome of dementia occurred in 1.4% of patients in both groups. The calibrated results from the Cox regression found no difference between the two groups (commercially insured database: calibrated HR = 0.69, 95% confidence interval = 0.45 to 1.05; Medicare‐only database: 1.14, 0.66 to 1.96). Results were similar in all sensitivity analyses: outcome of AD and including patients without RA. DISCUSSION: No significant difference for the risk of dementia or AD was seen between patients initiating a TNFI versus methotrexate. Although this study cannot conclude whether use of TNFIs is protective against dementia and AD compared with receiving no treatment, there was no evidence that it is more protective than the active comparator methotrexate. John Wiley and Sons Inc. 2021-09-20 /pmc/articles/PMC8450793/ /pubmed/34584936 http://dx.doi.org/10.1002/trc2.12163 Text en © 2021 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Kern, David M. Lovestone, Simon Cepeda, M. Soledad Treatment with TNF‐α inhibitors versus methotrexate and the association with dementia and Alzheimer's disease |
title | Treatment with TNF‐α inhibitors versus methotrexate and the association with dementia and Alzheimer's disease |
title_full | Treatment with TNF‐α inhibitors versus methotrexate and the association with dementia and Alzheimer's disease |
title_fullStr | Treatment with TNF‐α inhibitors versus methotrexate and the association with dementia and Alzheimer's disease |
title_full_unstemmed | Treatment with TNF‐α inhibitors versus methotrexate and the association with dementia and Alzheimer's disease |
title_short | Treatment with TNF‐α inhibitors versus methotrexate and the association with dementia and Alzheimer's disease |
title_sort | treatment with tnf‐α inhibitors versus methotrexate and the association with dementia and alzheimer's disease |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450793/ https://www.ncbi.nlm.nih.gov/pubmed/34584936 http://dx.doi.org/10.1002/trc2.12163 |
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