scholarly journals Mendelian randomization indicates that TNF is not causally associated with Alzheimer’s disease

2019 ◽  
Author(s):  
Shea J Andrews ◽  
Alison Goate
Keyword(s):  
Rheumatoid Arthritis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tumor Necrosis Factor ◽  
Causal Relationship ◽  
Tumor Necrosis ◽  
Mendelian Randomization ◽  
Potential Treatment ◽  
Tnf Α ◽  
Necrosis Factor

AbstractINTRODUCTIONEpidemiological research has suggested that inhibition of tumor necrosis factor (TNF)-α in patients with rheumatoid arthritis (RA) reduces the overall risk of Alzheimer’s disease (AD). TNF-α antagonists have been suggested as a potential treatment for AD.METHODSWe used a two-sample Mendelian randomization design to examine the causal relationship between blood TNF expression, serum TNF-α levels, and RA on AD risk.RESULTSOur results do not support a causal relationship between TNF expression, serum TNF-α levels or RA on AD risk.DISCUSSIONThese results suggest that TNF-α antagonists are unlikely to reduce the risk of AD.

scholarly journals Tumor necrosis factor α Inhibition for Alzheimer’s Disease

2017 ◽  
Vol 9 ◽  
pp. 117957351770927 ◽  
Author(s):  
Rudy Chang ◽  
Kei-Lwun Yee ◽  
Rachita K Sumbria
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Short Review ◽  
Tnf Α ◽  
Factor Α ◽  
Ad Therapy ◽  
Necrosis Factor

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

scholarly journals Tumor Necrosis Factor (TNF) Blocking Agents are Associated with Lower Risk for Alzheimer’s Disease in Patients with Rheumatoid Arthritis and Psoriasis

2019 ◽  
Author(s):  
Mengshi Zhou ◽  
Rong Xu ◽  
David C. Kaelber ◽  
Mark E. Gurney
Keyword(s):  
Rheumatoid Arthritis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tumor Necrosis Factor ◽  
Lower Risk ◽  
Tumor Necrosis ◽  
Blocking Agent ◽  
Retrospective Case ◽  
Tnf Blocker ◽  
Necrosis Factor

AbstractThis 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 is associated with lower risk for Alzheimer’s disease (AD) in patients with rheumatoid arthritis (RA), 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 AD as an outcome measure in patients receiving at least one prescription for a TNF blocking agent (etanercept, adalimumab, and infliximab) or for methotrexate. Adjusted odds ratios (AORs) were estimated using the Cochran-Mantel-Haenszel (CMH) method and presented with 95% confidence intervals (CIs) and p-values. RA was associated with a higher risk for AD (Adjusted Odds Ratio (AOR) = 2.06, 95% Confidence Interval: (2.02-2.10), P-value <0.0001) as did psoriasis (AOR = 1.37 (1.31-1.42), P <0.0001), ankylosing spondylitis (AOR = 1.57 (1.39-1.77), P <0.0001), inflammatory bowel disease (AOR = 2.46 (2.33-2.59), P < 0.0001), ulcerative colitis (AOR = 1.82 (1.74-1.91), P <0.0001), and Crohn’s disease (AOR = 2.33 (2.22-2.43), P <0.0001). The risk for AD in patients with RA was lower among patients treated with etanercept (AOR = 0.34 (0.25-0.47), P <0.0001), adalimumab (AOR = 0.28 (0.19-0.39), P < 0.0001), or infliximab (AOR = 0.52 (0.39-0.69), P <0.0001). Methotrexate was also associated with a lower risk for AD (AOR = 0.64 (0.61-0.68), P <0.0001), while lower risk was found in patients with a prescription history for both a TNF blocker and methotrexate. Etanercept and adalimumab also were associated with lower risk for AD 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 identifies a subset of patients in whom systemic inflammation contributes to risk for AD through a pathological mechanism involving TNF and who therefore may benefit from treatment with a TNF blocking agent.

scholarly journals Microglial derived tumor necrosis factor-α drives Alzheimer's disease-related neuronal cell cycle events

2014 ◽  
Vol 62 ◽  
pp. 273-285 ◽  
Author(s):  
Kiran Bhaskar ◽  
Nicole Maphis ◽  
Guixiang Xu ◽  
Nicholas H. Varvel ◽  
Olga N. Kokiko-Cochran ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Neuronal Cell ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Safety and Effectiveness of Rituximab in Patients with Rheumatoid Arthritis Following an Inadequate Response to 1 Prior Tumor Necrosis Factor Inhibitor: The RESET Trial

2011 ◽  
Vol 38 (12) ◽  
pp. 2548-2556 ◽  
Author(s):  
BOULOS HARAOUI ◽  
MARIA BOKAREWA ◽  
IAN KALLMEYER ◽  
VIVIAN P. BYKERK
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Patient Reported Outcomes ◽  
Tumor Necrosis ◽  
Primary Treatment ◽  
Tnf Α ◽  
Patient Reported ◽  
Infusion Reactions ◽  
Moderate Nausea ◽  
Necrosis Factor

Objective.To evaluate the safety and effectiveness of rituximab (RTX) in combination with methotrexate in patients with active rheumatoid arthritis (RA) after failure of a single tumor necrosis factor-α (TNF-α) inhibitor. Changes in patient-reported outcomes after primary treatment or retreatment with RTX and factors determining retreatment in clinical practice were also evaluated.Methods.In this phase 3b open-label, multicenter trial, patients received 2 slow infusions of RTX 1000 mg 14 days apart after premedication (primary treatment). Patients with a clinically relevant response could receive retreatment between 24 and 48 weeks. The primary endpoint was evaluation of safety. Secondary outcomes were safety of retreatment, effectiveness of primary treatment and retreatment, and changes in patient-reported outcomes after primary treatment or retreatment.Results.Of 120 patients enrolled at 36 centers and receiving primary RTX treatment, 77 received retreatment, 112 completed the 24-week primary treatment period, and 25 completed the 48-week primary treatment and retreatment period following a single course of RTX. The most common adverse events were mild to moderate nausea, vomiting, nasopharyngitis, and headache. No infections or infusion reactions were considered life-threatening. At 24 weeks, 58%, 27%, and 7% of patients achieved American College of Rheumatology 20, 50, and 70 improvements, respectively, and similar improvements were seen after retreatment.Conclusion.RTX was well tolerated, with a low incidence of infusion reactions and infections. Efficacy results, including enhanced response in rheumatoid factor-positive patients, were comparable to those reported in the literature. Based on its efficacy and safety profile and retreatment schedule, RTX is an attractive treatment option for patients that have not responded to a single TNF-α inhibitor.

Sign in / Sign up

Export Citation Format

Share Document