Treatment with TNF-α inhibitors versus methotrexate and the association with dementia and Alzheimer's disease.
Treatment with TNF-α inhibitors versus methotrexate and the association with dementia and Alzheimer's disease.
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DOI：
10.1002/trc2.12163
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Cepeda MS
中科院分区：
文献类型：
--
作者：
Kern DM;Lovestone S;Cepeda MS
肿瘤坏死因子-α在中枢神经系统外的外周抑制可能导致阿尔茨海默病(AD)预后的临床改善。肿瘤坏死因子-α抑制剂是治疗各种自身免疫性疾病的有效药物，可有效预防和/或治疗阿尔茨海默病。这项研究的目的是比较服用氨甲喋呤的患者和服用TNFIs的患者患痴呆症和AD的风险。来自商业保险和符合医疗保险条件的患者数据库的保险索赔数据被用来评估类风湿性关节炎(RA)患者启动TNFi与启动甲氨蝶呤的痴呆症和AD的风险。敏感性分析包括所有没有类风湿关节炎诊断要求的患者。风险期从索引日期到诊断结果、失访或收到对照药物为止。患者使用倾向评分进行1比1的匹配。采用Cox比例风险模型估计危险比(HR)。采用阴性对照对结果进行校正。总共确定了11,092名新的TNFi患者和44,023名新的甲氨蝶呤患者，每组中有8925名患者匹配。两组患者中均有1.4%的患者发生痴呆。Cox回归的校准结果发现两组之间没有差异(商业保险数据库：校准后的HR系数=0.69，95%可信区间=10.45至1.05；仅医疗保险数据库：1.14，0.66至1.96)。在所有敏感性分析中，结果都是相似的：AD的结局和包括没有RA的患者。在启动TNFi的患者和甲氨蝶呤患者之间，痴呆症或AD的风险没有显著差异。虽然这项研究不能得出结论，与不接受治疗相比，使用TNFIs是否对痴呆症和AD具有保护作用，但没有证据表明它比活性比较剂甲氨蝶呤更有保护作用。
Peripheral inhibition of tumor necrosis factor (TNF)‐α, outside of the central nervous system, may result in clinical improvement of Alzheimer's disease (AD) outcomes. TNF‐α inhibitors (TNFIs) are effective treatments for various autoimmune conditions and may be effective for preventing and/or treating AD. The objective of this study was to compare the risk of dementia and AD in patients initiating methotrexate versus those initiating TNFIs. Insurance claims data from databases of commercially insured and Medicare‐eligible patients were used to estimate the risk of dementia and AD within patients with rheumatoid arthritis (RA) initiating a TNFI versus initiation of methotrexate. A sensitivity analysis included all patients without the RA diagnosis requirement. The at‐risk period spanned from the index date until a diagnosis of the outcome, loss‐to‐follow‐up, or receipt of the comparator drug. Patients were matched 1‐to‐1 using propensity scores. A Cox proportional hazards model was used to estimate the hazard ratio (HR). Negative controls were used to calibrate the results. A total of 11,092 new TNFI patients and 44,023 new methotrexate patients were identified, and 8925 from each group were matched. The outcome of dementia occurred in 1.4% of patients in both groups. The calibrated results from the Cox regression found no difference between the two groups (commercially insured database: calibrated HR = 0.69, 95% confidence interval = 0.45 to 1.05; Medicare‐only database: 1.14, 0.66 to 1.96). Results were similar in all sensitivity analyses: outcome of AD and including patients without RA. No significant difference for the risk of dementia or AD was seen between patients initiating a TNFI versus methotrexate. Although this study cannot conclude whether use of TNFIs is protective against dementia and AD compared with receiving no treatment, there was no evidence that it is more protective than the active comparator methotrexate.
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影响因子：
105.7
作者：
Etminan, M;Gill, S;Samii, A
通讯作者：
Samii, A
影响因子：
2
作者：
Schuemie, Martijn J.;Ryan, Patrick B.;DuMouchel, William;Suchard, Marc A.;Madigan, David
通讯作者：
Madigan, David
DOI：
10.1097/ede.0b013e3181d61eeb
发表时间：
2010-05
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Lipsitch M;Tchetgen Tchetgen E;Cohen T
通讯作者：
Cohen T
影响因子：
2
作者：
Austin, Peter C.
通讯作者：
Austin, Peter C.
影响因子：
4.2
作者：
Rogers, J;Webster, S;McGeer, P
通讯作者：
McGeer, P