New findings from the ongoing Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study suggest that certain rheumatoid arthritis drugs may lower incidences of Alzheimer’s disease and related dementias in people with cardiovascular disease. While the findings do not support the broad use of these drugs for treating Alzheimer’s and related dementias, the results may point to a promising precision-medicine approach in specific groups of people at risk for developing these diseases.
The research was published in JAMA Network Open and led by NIA scientists in collaboration with researchers at Harvard Medical School, Boston; Rutgers University, New Brunswick, New Jersey; and Johns Hopkins University School of Medicine, Baltimore.
Discovering new drug targets in Alzheimer’s and related dementias is crucial for meeting the enormous public health challenge of these diseases. Prior studies on whether approved rheumatoid arthritis drugs lower the risk of developing dementia have produced mixed results. The ongoing NIA DREAM study previously identified several FDA-approved drugs that are being tested as candidate treatments for Alzheimer’s and related dementias.
In this study, researchers analyzed data in Medicare claims from more than 22,000 people aged 65 years and older from 2007 to 2017, looking at whether those with rheumatoid arthritis who took one of three different classes of arthritis drugs were protected from dementia.
Researchers found that there were no statistically significant associations with lowered dementia risk except among those with cardiovascular disease who were treated with one class of arthritis drugs called TNF inhibitors. These inhibitors suppress the immune system by blocking the activity of TNF, which is a substance in the body that can cause inflammation and lead to immune-system diseases, including rheumatoid arthritis. Moreover, a recent large Genome-Wide Association Study (GWAS) discovered genetic risk variants related to TNF signaling to be associated with the risk of Alzheimer’s, suggesting that abnormalities in this pathway may be causally related to the disease. Together, these findings demonstrate the importance of generating valid, actionable evidence on drug repurposing using routine health care data.
An important limitation is that the development of Alzheimer’s and related dementias may begin many years before a clinical diagnosis. Given this, longer periods of treatment and/or observation may be needed to draw firmer conclusions about the null findings. Additionally, although the researchers strived to address limitations related to identifying Alzheimer’s and related dementias in health care claims through their careful study design, there remains a possibility of bias from outcome misclassification.
This research was supported by NIA Intramural Research Program project 1ZIAAG000436-01.
These activities relate to NIA’s AD+ADRD Milestone 7.B, “Initiate research programs for translational bioinformatics and network pharmacology to support rational drug repositioning and combination therapy from discovery through clinical development.”
References: Desai R, et al. Comparative Risk of Alzheimer Disease and Related Dementia Among Medicare Beneficiaries With Rheumatoid Arthritis Treated With Targeted Diseases-Modifying Antirheumatic Agents. JAMA Network Open. 2022;5(4):e226567. doi:10.1001/jamanetworkopen.2022.6567.