A large, retrospective case-control study of electronic health records from 56 million unique adult patients examined whether or not treatment with a Tumor Necrosis Factor ( TNF ) blocking agent reduced risk for Alzheimer's disease in patients with rheumatoid arthritis, psoriasis, and other inflammatory diseases which are mediated in part by TNF and for which a TNF blocker is an approved treatment.
The analysis compared the diagnosis of Alzheimer's disease as an outcome measure in patients receiving at least one prescription for a TNF blocking agent ( Etanercept [ Enbrel ], Adalimumab [ Humira ], and Infliximab [ Remicade ] ) or for Methotrexate.
Rheumatoid arthritis increased the risk for Alzheimer's disease ( Adjusted Odds Ratio [ AOR ] = 2.06, 95% Confidence Interval: ( 2.02-2.10 ), P-value less than 0.0001 ) as did psoriasis ( AOR = 1.37 [ 1.31-1.42 ], P less than 0.0001 ), ankylosing spondylitis ( AOR = 1.57 [ 1.39-1.77 ], P less than 0.0001 ), inflammatory bowel disease ( AOR = 2.46 [ 2.33-2.59 ], P less than 0.0001 ), ulcerative colitis ( AOR = 1.82 [ 1.74-1.91 ], P less than 0.0001 ), and Crohn's disease ( AOR = 2.33 [ 2.22-2.43 ], P less than 0.0001 ).
The risk for Alzheimer's disease in patients with rheumatoid arthritis was reduced by treatment with Etanercept ( AOR = 0.34 [ 0.25-0.47 ], P less than 0.0001 ), Adalimumab ( AOR = 0.28 [ 0.19-0.39 ], P less than 0.0001 ), and Infliximab ( AOR = 0.52 [ 0.39-0.69 ], P less than 0.0001 ).
Methotrexate also reduced risk for Alzheimer's disease ( AOR = 0.64 [ 0.61-0.68 ], P less than 0.0001 ), while further risk reduction was achieved in patients with a prescription history for both a TNF blocker and Methotrexate.
Etanercept and Adalimumab also reduced the risk for Alzheimer's disease in patients with psoriasis ( AOR = 0.47 [ 0.30-0.73 ] and 0.41 [ 0.20-0.76 ], respectively.
There was no effect of gender or race, while younger patients showed greater benefit from a TNF blocker than did older patients.
This study has identified a subset of patients in whom systemic inflammation contributes to risk for Alzheimer's disease through a pathological mechanism involving TNF and who therefore may benefit from treatment with a TNF blocking agent. ( Xagena )
Source: MedRxiv 2019; DOI: 10.1101/19007666