Retrospective Study of 56 Million Patients Shows Reduced Risk of Alzheimer With Anti-TNF Use

Researchers from biotech company Tetra Therapeutics have reported that, in their retrospective population-based study of 56 million patients with inflammatory diseases, use of anti—tumor necrosis factor (anti-TNF) agents was linked with a reduced risk of Alzheimer disease.

The study, which Tetra Therapeutics conducted together with Case Western Reserve University, used deidentified electronic health records collected by the IBM Watson Health Explorys Cohort Discovery platform that serves 360 hospitals and 317,000 providers.

Data were included from patients who had rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis, psoriatic arthritis (PsA), and inflammatory bowel diseases (IBD) including ulcerative colitis (UC) and Crohn disease (CD). The researchers sought to assess whether these diseases themselves increased the risk for Alzheimer, and whether risk could be mitigated through blocking TNF.

They found that the risk of Alzheimer was increased in adults with RA (adjusted odds ratio [OR], 2.06; 95% CI, 2.02-2.10), psoriasis (adjusted OR, 1.37; 95% CI, 1.31-1.42), AS (adjusted OR, 1.57; 95% CI, 1.39-1.77), IBD (adjusted OR 2.46, 95% CI, 2.33-2.59), UC (adjusted OR, 1.82; 95% CI, 1.74-1.91), and CD (adjusted OR, 2.33; 95% CI, 2.22-2.43).

Anti-TNF use was linked with reduced Alzheimer risk; in patients with RA who were treated with etanercept, the adjusted OR was 0.34 (95% CI, 0.25-0.47). Those who took adalimumab had an adjusted OR of 0.28 (95% CI, 0.19-0.39), and those who took infliximab had an adjusted OR of 0.52 (95% CI, 0.39-0.69).

Patients with psoriasis who took etanercept (adjusted OR, 0.47; 95% CI, 0.30-0.73) or adalimumab (adjusted OR, 0.41; 95% CI, 0.20-0.76) also had a reduced risk.

Younger patients showed a greater benefit from anti-TNF therapy than older patients, but sex and race did not impact the results. Methotrexate use was also associated with a reduced risk in RA, particularly among patients who took both methotrexate and an anti-TNF therapy.

“The study findings are exciting in that we clearly see that TNF blocking agents reduce the risk for comorbid Alzheimer’s disease in real-world patients diagnosed with [RA] or psoriasis,” said Rong Xu, PhD, associate professor, Department of Population and Quantitative Health Sciences, School of Medicine at Case Western Reserve University and coauthor of the study, in a statement.

“Given that anti-TNF biologics are powerful drugs, we believe further prospective studies are necessary to understand their potential in treating or preventing Alzheimer's disease,” added Xu.

The company will present the findings during a poster session at the 12th Clinical Trials on Alzheimer’s Disease Meeting being held this week in San Diego, California.

Earlier this year, The Washington Post reported that etanercept, sold as the blockbuster rheumatoid arthritis drug Enbrel by Amgen within the United States and by Pfizer in other territories, appeared to reduce the risk of Alzheimer disease. Researchers urged the company to conduct a clinical trial, but after several years of discussion, Pfizer opted not to pursue that path, deeming that it held little chance of success. A trial could have cost approximately $80 million, according to reports, and would have made little financial sense given the upcoming patent expirations on Enbrel and eventual biosimilar competition.