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The link between arthritis drug use and Alzheimer’s disease risk

According to the results of a study published in Open JAMA Network.

SARD affects more than 5 million people in the United States, and disease-modifying treatment options are limited. The Drug Repurposing for Effective Alzheimer Medicines (DREAM) initiative was a study designed to identify drugs that could be repurposed for the treatment of Alzheimer’s disease. Previously, tofacitinib, tocilizumab, and TNF therapies were thought to be potential treatments for MADR. For this study, the researchers aimed to assess whether there is evidence from real world data indicating whether any of these therapies were associated with a risk of ADHD.

Researchers at Brigham and Women’s Hospital drew 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 to those who received abatacept for incidence rates of MADR. A 1:1 propensity-matching method was used to balance the patient cohorts, and the risk of MADR was assessed using four approaches that assessed MADR during treatment (analysis 1), reverse causation of ADRD (analysis 2), delayed diagnosis of ADRD (analysis 3) and ADRD misclassification (analysis 4).

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The tofacitinib (n=4224), tocilizumab (n=6369), and TNF inhibitor (n=11,976) cohorts with their propensity-matched abatacept cohorts averaged 71.99 to 72 years of age, 68 years, 79.1%-82.4% were female and 80.5%-87.0% were white.

According to MADR risk analyses, the incidence rate of MAAD ranged from 2-4 per 1000 person-years to 14-18 per 1000 person-years.

Tofacitinib was not analyzed in any analysis (analysis 1: RR, 0.90; 95% CI, 0.55-1.51; analysis 2: RR, 0.78; 95% CI, 0.53 -1.13; analysis 3: RR, 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: RR 1.02 95% CI 0.86-1.20 Analysis 3 RR 1.13 95% CI 0 .86-1.48; Analysis 4: RR, 0.90; 95% CI, 0.60-1.37) significantly associated with ADHD risk.

In subgroup analyses, patients who had baseline cardiovascular disease and received TNF inhibitors had a reduced risk of ADRD in analyzes 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 MADR, and longer treatment or observation periods may have been required to monitor effects.

“These findings do not support the promotion of targeted disease-modifying antirheumatic drugs as disease-modifying candidates for MADR,” the researchers concluded.

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


Desai RJ, Varma VR, Gerhard T, et al. Comparative risk of Alzheimer’s disease and related dementia in 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