Disease-Modifying Antirheumatic Drugs and Dementia Prevention: A Systematic Review of Observational Evidence in Rheumatoid Arthritis

C.-Y. Wu, L. Y. Xiong, Y. Y. Wong, S. Noor, G. Bradley-Ridout, Walter Swardfager
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Abstract

Background

Many observational studies have examined the association of disease-modifying antirheumatic drugs (DMARDs) with dementia risk, but the evidence has been mixed, possibly due to methodological reasons. This systematic review (PROSPERO: CRD42023432122) aims to assess existing observational evidence and to suggest if repurposing DMARDs for dementia prevention merits further investigation.

Methods

Four electronic databases up to October 26, 2023, were searched. Cohort or case-control studies that examined dementia risk associated with DMARDs in people with rheumatoid arthritis were included. Risk of bias was evaluated using the Cochrane Collaboration’s Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) criteria. Findings were summarized by individual drug classes and by risk of bias.

Results

Of 12,180 unique records, 14 studies (4 case-control studies, 10 cohort studies) were included. According to the ROBINS-I criteria, there were 2 studies with low risk of bias, 1 study with moderate risk, and 11 studies with serious or critical risk. Among studies with low risk of bias, one study suggested that hydroxychloroquine versus methotrexate was associated with lower incident dementia, and the other study showed no associations of tumor necrosis factor (TNF) inhibitors, tocilizumab, and tofacitinib, compared to abatacept, with incident dementia.

Conclusion

Studies that adequately addressed important biases were limited. Studies with low risk of bias did not support repurposing TNF inhibitors, tocilizumab, abatacept or tofacitinib for dementia prevention, but hydroxychloroquine may be a potential candidate. Further studies that carefully mitigate important sources of biases are warranted, and long-term evidence will be preferred.

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改变病情的抗风湿药物与痴呆症的预防:类风湿关节炎观察证据的系统回顾
背景许多观察性研究探讨了改变病情抗风湿药(DMARDs)与痴呆风险之间的关系,但可能由于方法学方面的原因,相关证据参差不齐。本系统综述(PROSPERO:CRD42023432122)旨在评估现有的观察性证据,并提出是否值得进一步研究将 DMARDs 用于痴呆症预防。方法检索了截至 2023 年 10 月 26 日的四个电子数据库,纳入了对类风湿关节炎患者使用 DMARDs 相关痴呆症风险进行研究的队列研究或病例对照研究。采用 Cochrane 协作组织的非随机干预研究偏倚风险(ROBINS-I)标准对偏倚风险进行了评估。结果 在 12180 条记录中,共纳入了 14 项研究(4 项病例对照研究和 10 项队列研究)。根据 ROBINS-I 标准,2 项研究存在低偏倚风险,1 项研究存在中度偏倚风险,11 项研究存在严重或临界偏倚风险。在偏倚风险较低的研究中,一项研究表明羟氯喹与甲氨蝶呤相比与较低的痴呆发病率有关,另一项研究表明肿瘤坏死因子(TNF)抑制剂、托西珠单抗和托法替尼与阿帕他赛相比与痴呆发病率无关。偏倚风险较低的研究不支持将TNF抑制剂、托西珠单抗、阿帕赛普或托法替尼重新用于痴呆症的预防,但羟氯喹可能是一个潜在的候选药物。有必要开展进一步的研究,仔细减少重要的偏倚来源,并优先考虑长期证据。
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The Journal of Prevention of Alzheimer's Disease
The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health
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期刊介绍: The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.
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