Dementia more common in patients with RA receiving csDMARDs vs b/tsDMARDs
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Dementia is more common in patients with rheumatoid arthritis who receive conventional synthetic disease modifying anti-rheumatic drugs vs. biologics or targeted synthetic treatments, according to data.
“Neuroinflammation, a chronic process of local sustained inflammation secondary to either intrinsic or systemic stimuli, is thought to play an important role in the development of dementia, particularly Alzheimer's dementia (AD),” Sebastian E. Sattui, MD, MS, of the University of Pittsburgh, and colleagues wrote in Seminars in Arthritis and Rheumatism. “The role of tumor necrosis factor-alpha (TNF-) in the development of dementia has been particularly highlighted, raising an interest for the potential protective effect of TNF- inhibitors (TNFi).
“Biological (eg, elevated proinflammatory cytokines, increased blood-brain barrier permeability, premature immunosenescence) and clinical factors (eg, chronic pain, depression, disability, cardiovascular disease) represent potential and biologically-plausible links between cognitive decline and rheumatoid arthritis,” they added. “Few studies have investigated the effect of disease modifying antirheumatic drugs (DMARDs), including TNFi-bDMARDs, and incident dementia in patients with RA.”
To investigate the risk for dementia in patients with RA receiving biologic or targeted synthetic DMARDs, compared with conventional synthetic DMARDs, Sattui and colleagues evaluated CMS claims data from 2006 to 2017. To be included, patients must have been diagnosed with RA and continued enrollment in Medicare fee for service for at least 12 months prior to the baseline period of disease presentation. Patients were excluded if they had dementia at baseline or other rheumatic diseases. Patients with end-stage renal disease, cancer and HIV or AIDS were also excluded.
The researchers used pharmacy and medical claims data to establish periods of drug exposure. Specifically, they assessed biologic or targeted synthetic DMARDs, with or without conventional synthetic DMARDs, or conventional synthetic DMARDs alone. Primary outcomes included incident dementia or a prescription for dementia-specific medication. The researchers used diagnostic and drug codes to identify these cases.
The analysis included 141,326 eligible patients with RA. In all, there were 233,271 DMARD initiations and 3,794 cases of incident dementia during the study period.
According to the researchers, the incident rate of dementia was two per 100 person-years for patients receiving conventional synthetic DMARDs (95% CI, 1.9-2.1) vs. 1.3 per 100 person-years for patients using any biologic or targeted synthetic DMARD (95% CI, 1.2-1.4). This resulted in a 19% lower risk for patients receiving biologic or targeted synthetic DMARDs, compared with those receiving conventional synthetic DMARDs (HR = 0.81; 95% CI, 0.76-0.87).
“Among Medicare beneficiaries with RA, b/tsDMARDs were associated with a lower risk of incident dementia when compared to patients on csDMARDs only even after adjusting for relevant covariates,” Sattui and colleagues wrote. “The decreased risk of incident dementia was observed irrespective of type of b/tsDMARDs use and was consistent in the subgroup analysis of patients who had been taking [methotrexate] previously or patients with or without [cardiovascular] risk factors or [cardiovascular disease].”
References:
- Newcombe EA, et al. J Neuroinflamm. 2015;doi: 10.1186/s12974-018-1313-3
- Pasqualetti G, et al. Curr Neurol Neurosci Rep. 2015;doi: 10.1007/s11910-015-0531-7
- Torres-Acosta N, et al. J Alzheimer's Dis. 2020;doi: 10.3233/JAD-200711
Perspective
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Rheumatoid arthritis is well known to have systemic effects in addition to its impact on the joints. Considering the connections between chronic sustained neuroinflammation and dementia, it is not surprising that the sustained systemic inflammation involved with RA would predispose a patient to diseases like Alzheimer’s. Preventative health screenings, such as mini mental examinations, are simple but important diagnostic tools to screen for changes in the cognitive health of patients to detect signs of dementia.
Advanced practice providers have an opportunity to fill in the gaps caring for patients with rheumatic disease coupled with various preventative health screening tools to guide treatment. Detecting cognitive decline in patients with active severe RA may can change the direction of the treatment plan with biologics or targets synthetic DMARDs to help reduce inflammation, thus reducing those extra articular manifestations that lead to increased morbidities and mortalities such as dementia.
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