Anti-TNF Agents May Lower Alzheimer Disease Risk for Patients With Psoriasis, Rheumatoid Arthritis

A subset of patients at risk for Alzheimer disease because of systemic inflammation may benefit from receiving a tumor necrosis factor (TNF) blocking agent.

Exposure to tumor necrosis factor (TNF) blocking agents may reduce the risk for Alzheimer disease in patients with inflammatory disease, study data published in PLoS One suggests. In this large, retrospective study of electronic health records, patients receiving anti-TNF drugs for psoriasis or rheumatoid arthritis (RA) displayed significantly decreased risk for Alzheimer disease compared with patients receiving no medication.

Investigators abstracted de-identified health records data from the IBM Watson Health Explorys Cohort Discovery platform. The Explorys platform harmonizes data from 360 hospitals and 317,000 providers around the United States. Collected data include patient demographics, disease diagnoses, medication history, surgical history, and laboratory figures. Eligible patients had a diagnosis of 1 of 8 inflammatory diseases: RA, psoriasis, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease, ulcerative colitis, or Crohn’s disease. Medication exposure was determined by outpatient prescription records. Patients were considered cases if they were taking 1 of 5 anti-TNF agents: etanercept, adalimumab, infliximab, certolizumab pegol, or golimumab. Controls were patients not taking any medication for their inflammatory disease. Patients with more than 1 inflammatory disease diagnosis and patients taking more than 1 TNF blocker were excluded. The primary outcome measure was clinician-diagnosed Alzheimer disease. Adjusted odds ratios (aORs) for Alzheimer disease were estimated using the Cochrane-Mantel-Haenszel method for cases and controls. The odds of Alzheimer disease were also compared between patients with inflammatory disease and control patients without disease.

The study population comprised records from 55,902,250 unique adult patients (≥18 years), of whom 54.88% were women. The majority of patients were white (57.75%) and between 18 to 65 years of age (70.25%). The prevalence of each inflammatory disease diagnosis ranged from 0.060% (ankylosing spondylitis) to 0.92% (RA). Overall, 338,400 patients (0.60%) were diagnosed with Alzheimer disease. Compared with patients without inflammatory disease, the risk for Alzheimer disease was substantially greater in  patients with RA (aOR, 2.06; 95% confidence interval [CI], 2.02-2.10; P <.0001), psoriasis (aOR, 1.37; 95% CI, 1.31-1.42), ankylosing spondylitis (aOR, 1.57; 95% CI, 1.39-1.77), inflammatory bowel disease (aOR, 2.46; 95% CI, 2.33-2.59), ulcerative colitis (aOR, 1.83; 95% CI, 1.74-1.91), and Crohn’s disease (aOR, 2.33; 95% CI, 2.22-2.43) (all P <.0001). Alzheimer disease risk for patients with RA was lower for those treated with etanercept (aOR, 0.34; 95% CI, 0.25-0.47), adalimumab (aOR, 0.28; 95% CI, 0.19-0.39), and infliximab (aOR, 0.52; 95% CI, 0.39-0.69) compared with those not receiving medication at all (all P <.0001). Methotrexate, although not a TNF blocker, also appeared to decrease risk for patients with RA compared with no medication (aOR, 0.64; 95% CI, 0.61-0.68). In patients with psoriasis, treatment with etanercept (aOR, 0.47; 95% CI, 0.30-0.73) and adalimumab (aOR, 0.41; 95% CI, 0.20-0.76) appeared to decrease Alzheimer disease risk, although treatment with infliximab and methotrexate did not. When patients were stratified by gender, age, and race, the risk-reducing effects of TNF blockers appeared to be stronger in  white vs non-white patients and in  younger (18-65 years) vs older (>65 years) patients. Insurance status did not appear to mediate the effect of anti-TNF agents.

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These data suggest that anti-TNF agents may have a protective effect against Alzheimer disease development in patients with RA and psoriasis. Methotrexate may also have an appreciable risk-reducing effect for patients with RA. Due to the small percentage of patients with other inflammatory diseases, the effects of TNF blockers could not be explored in patients with diagnoses other than RA or psoriasis. In addition, medication adherence could not be confirmed from health record data; results must be extrapolated with care. Despite these limitations, these data identify a certain subset of patients with inflammatory disease who may benefit from anti-TNF treatment as a means of Alzheimer disease prevention. In addition, results suggest that the development of Alzheimer disease in patients with systemic inflammation likely occurs through a pathway which involves TNF.

Disclosure: One study author declared affiliations with the pharmaceutical industry.

Please see the original reference for a full list of authors’ disclosures.

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Zhou M, Xu R, Kaelber DC, Gurney ME. Tumor necrosis factor (TNF) blocking agents are associated with lower risk for Alzheimer’s disease in patients with rheumatoid arthritis and psoriasis [published online March 23, 2020]. PLoS One. doi: 10.1371/journal.pone.0229819