Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis
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)...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-02-01
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| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/10/1/e004016.full |
| _version_ | 1797221900845318144 |
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| author | Wenhui Xie Shiyu Xiao Zhuoli Zhang Xiaolin Zhang Yue Hou |
| author_facet | Wenhui Xie Shiyu Xiao Zhuoli Zhang Xiaolin Zhang Yue Hou |
| author_sort | Wenhui Xie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T21:12:11Z |
| format | Article |
| id | doaj.art-6599a6e3389841c3b045ca333a033a8d |
| institution | Directory Open Access Journal |
| issn | 2056-5933 |
| language | English |
| last_indexed | 2024-04-24T13:12:47Z |
| publishDate | 2024-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | RMD Open |
| spelling | doaj.art-6599a6e3389841c3b045ca333a033a8d2024-04-05T03:05:08ZengBMJ Publishing GroupRMD Open2056-59332024-02-0110110.1136/rmdopen-2023-004016Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysisWenhui Xie0Shiyu Xiao1Zhuoli Zhang2Xiaolin Zhang3Yue Hou4Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, ChinaDepartment of Gastroenterology, University of Electronic Science and Technology, Chengdu, ChinaDepartment of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, ChinaGeriatric Department, Peking University First Hospital, Beijing, ChinaDepartment of Geriatrics, Peking University First Hospital, Beijing, ChinaBackground 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.https://rmdopen.bmj.com/content/10/1/e004016.full |
| spellingShingle | Wenhui Xie Shiyu Xiao Zhuoli Zhang Xiaolin Zhang Yue Hou Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis RMD Open |
| title | Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis |
| title_full | Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis |
| title_fullStr | Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis |
| title_full_unstemmed | Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis |
| title_short | Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis |
| title_sort | association between disease modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia a systematic review with meta analysis |
| url | https://rmdopen.bmj.com/content/10/1/e004016.full |
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