The Link Between the Use of Arthritis Drugs and Alzheimer Disease Risk

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Researchers sought to evaluate whether there is any evidence from real-world data on treatment with tofacitinib, tocilizumab, or tumor necrosis factor and the risk for ADRD.

The risk for Alzheimer disease and related dementia (ADRD) appeared to be lower among patients with arthritis with cardiovascular disease who were treated with tofacitinib, tocilizumab, or tumor necrosis factor (TNF) inhibitor therapy, according to study findings published in JAMA Network Open.

ADRD affects over 5 million people in the US and there are limited disease-modifying treatment options available. The Drug Repurposing for Effective Alzheimer Medicines (DREAM) initiative was a study designed to identify drugs which could be repurposed for ADRD treatment. Previously, tofacitinib, tocilizumab, and TNF therapies were hypothesized to be potential treatments for ADRD. For this study, the researchers aimed to evaluate whether there is any evidence from real-world data about whether any of these therapies were associated with risk for ADRD.

Researchers from Brigham and Women’s Hospital sourced data for this study from Medicare fee-for-service claims data. Between 2007 and 2017, patients who received tofacitinib, tocilizumab, or TNF inhibitors for rheumatoid arthritis (RA) were compared with those who received abatacept for incidence rates of ADRD. A 1:1 propensity matching method was used to balance patient cohorts and risk for ADRD was evaluated using four approaches which assessed ADRD during treatment (analysis 1), reverse causation for ADRD (analysis 2), delayed ADRD diagnosis (analysis 3), and ADRD misclassification (analysis 4).

The tofacitinib (n=4224), tocilizumab (n=6369), and TNF inhibitor (n=11,976) cohorts with their propensity matched abatacept cohorts were aged mean 71.99-72.68 years, 79.1%-82.4% were women, and 80.5%-87.0% were White.

Depending on the ADRD risk analyses, the incidence rate of ADRD ranged from 2-4 per 1000 person-years to 14-18 per 1000 person-years.

In no analyses were tofacitinib (analysis 1: HR, 0.90; 95% CI, 0.55-1.51; analysis 2: HR, 0.78; 95% CI, 0.53-1.13; analysis 3: HR, 1.29; 95% CI, 0.72-2.33; analysis 4: HR, 0.50; 95% CI, 0.21-1.20), tocilizumab (analysis 1: HR, 0.82; 95% CI, 0.55-1.21; analysis 2: HR, 1.05; 95% CI, 0.81-1.35; analysis 3: HR, 1.21; 95%CI, 0.75-1.96]; analysis 4: HR, 0.78; 95% CI, 0.44-1.39), or TNF inhibitors (analysis 1: HR, 0.93; 95% CI, 0.72-1.20; analysis 2: HR, 1.02; 95% CI, 0.86-1.20; analysis 3: HR, 1.13; 95% CI, 0.86-1.48; analysis 4: HR, 0.90; 95% CI, 0.60-1.37) significantly associated with ADRD risk.

In subgroup analyses, patients who had baseline cardiovascular disease and received TNF inhibitors were at decreased risk for ADRD in analysis 2 (HR, 0.74; 95% CI, 0.56-0.99) and 4 (HR, 0.45; 95% CI, 0.21-0.98).

Study limitations included the prolonged preclinical phase of ADRD, and longer periods of treatment or observation may have been needed to monitor the effects.

“These results do not support advancing targeted disease-modifying antirheumatic drugs as disease modifying candidates for ADRD,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Desai RJ, Varma VR, Gerhard T, et al. Comparative Risk of Alzheimer Disease and Related Dementia Among Medicare Beneficiaries With Rheumatoid Arthritis Treated With Targeted Disease-Modifying Antirheumatic Agents. JAMA Netw Open. 2022;5(4):e226567. doi:10.1001/jamanetworkopen.2022.6567