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Abstract
Background Dysregulation of several inflammatory cytokines including tumour necrosis factor (TNF) in dementia patients has also been identified as a key factor in the pathogenesis of rheumatoid arthritis (RA). We aimed to investigate the association of disease-modifying antirheumatic drugs (DMARDs) therapy for RA with risk of incident dementia.
Methods Electronic database searches of PubMed, EMBASE and Cochrane Library were performed. Observational studies that assessed the association of dementia with DMARDs in RA were included. Pooled risk ratios (RRs) with 95% CIs were used as summary statistic. The certainty of evidence was judged by using the Grading of Recommendations Assessment, Development and Evaluation system.
Results Overall, 14 studies involving 940 442 patients with RA were included. Pooled RR for developing dementia was 0.76 (95% CI 0.72 to 0.80) in patients taking biological DMARDs overall versus those taking conventional synthetic DMARDs, with 24% for TNF inhibitors (RR 0.76, 95% CI 0.71 to 0.82), 24% for non-TNF biologics (RR 0.76, 95% CI 0.70 to 0.83), separately. There was a significant subgroup effect among different types of TNF inhibitors (RR 0.58 [95%CI 0.53 to 0.65], 0.65 [95% CI 0.59 to 0.72], 0.80 [95% CI 0.72 to 0.88] for etanercept, adalimumab, infliximab, respectively; p value between groups=0.002). However, compared with non-users of DMARDs or investigative treatment, no significant effect on dementia incidence was observed in those receiving conventional synthetic DMARDs overall (RR 0.84, 95% CI 0.59 to 1.20), methotrexate (RR 0.78, 95% CI 0.54 to 1.12), hydroxychloroquine (RR 0.95, 95% CI 0.63 to 1.44), except for sulfasalazine (RR 1.27, 95% CI 1.06 to 1.50).
Conclusions Biological DMARDs for RA are associated with decreased dementia risk, while protective effect is not observed in conventional synthetic DMARDs. Controlled clinical trials on TNF inhibitors are necessary to test their neuroprotective potentials.
- Rheumatoid Arthritis
- Biological Therapy
- Methotrexate
Data availability statement
Data are available on reasonable request.
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Data availability statement
Data are available on reasonable request.
Supplementary materials
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Footnotes
Presented at The present study was presented as a conference abstract in Annual Meeting of the European Alliance of Associations for Rheumatology, EULAR 2023 (https://ard.bmj.com/content/82/Suppl_1/860.2) and International Conference of Chinese Rheumatologists, ICCR 2023 (https://www.worldscientific.com/doi/10.1142/S266134172374022X).
Contributors Study conceptualisation: ZZ and WX; Study design: ZZ and WX; Data search: WX and YH; Data screener: ZZ, WX and YH; Data extraction: ZZ, WX and YH; Statistical analyses: WX, SX and XZ; Risk of bias assessment: ZZ, WX and YH; Quality of evidence assessment: ZZ, WX and YH; Adjudicator: ZZ; Write-up: WX and ZZ; Drafted and revised the manuscript for intellectual content. All authors have approved the final manuscript. ZZ is the guarantor of this study, accepting full responsibility for the work and the conduct of the study, had access to the data and controlled the decision to publish.
Funding This study was supported by the National Natural Science Foundation of China (82372369, 82302018) and the National High Level Hospital Clinical Research Funding (Scientific Research Seed Fund of Peking University First Hospital) (grant number: 2023SF48).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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