ImportanceTumor necrosis factor (TNF) inhibitors have been used extensively to treat various autoimmune diseases. However, there are ongoing debates about the risk of inflammatory central nervous system (CNS) disease events following TNF inhibitor therapy, as well as uncertainty about how this risk varies across different autoimmune diseases or TNF-blocking agents.ObjectiveTo evaluate the risk of inflammatory CNS diseases after anti-TNF initiation and assess the difference in risk among different types of underlying autoimmune diseases or TNF inhibitors.Data SourcesSeparate searches were conducted across PubMed, Embase, and the Cochrane Library from inception until March 1, 2024.Study SelectionObservational studies assessing the association between anti-TNF therapy and inflammatory CNS diseases relative to a comparator group.Data Extraction and SynthesisStudy eligibility assessment and data extraction were independently conducted by 2 investigators following PRISMA guidelines. The risk ratio (RR) was used as the effect measure of the pooled analysis.Main Outcomes and MeasuresThe primary outcome was the risk of incident inflammatory CNS events after anti-TNF therapy for autoimmune diseases. Secondary analyses were performed based on different types of underlying autoimmune diseases and TNF inhibitors.ResultsEighteen studies involving 1 118 428 patients with autoimmune diseases contributing more than 5 698 532 person-years of follow-up were analyzed. The incidence rates of new-onset inflammatory CNS events after initiating TNF inhibitors ranged from 2.0 to 13.4 per 10 000 person-years. Overall, exposure to TNF inhibitors was associated with a 36% increased risk of any inflammatory CNS disease compared to conventional therapies (RR, 1.36; 95% CI, 1.01-1.84; I2, 49%), mainly attributed to demyelinating diseases (RR, 1.38; 95% CI, 1.04-1.81; I2, 31%). Secondary analyses revealed a similar risk of inflammatory CNS diseases across different types of underlying autoimmune diseases (rheumatic diseases: RR, 1.36; 95% CI, 0.84-2.21; inflammatory bowel disease 1.49; 95% CI, 0.93-2.40; P for subgroup = .74) and TNF inhibitors (anti-TNF monoclonal antibodies vs etanercept: RR, 1.04; 95% CI, 0.93-1.15; I2, 0%).Conclusions and RelevanceCompared to conventional therapies, exposure to TNF inhibitors was associated with a 36% increased risk of inflammatory CNS diseases, irrespective of background autoimmune disease or TNF inhibitor type.

中文翻译：

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自身免疫性疾病肿瘤坏死因子抑制剂治疗后炎症性中枢神经系统疾病的风险


重要性肿瘤坏死因子 （TNF） 抑制剂已广泛用于治疗各种自身免疫性疾病。然而，关于 TNF 抑制剂治疗后炎症性中枢神经系统 （CNS） 疾病事件的风险，以及这种风险在不同自身免疫性疾病或 TNF 阻断剂之间如何变化的不确定性，仍然存在持续的争论。目的评估抗 TNF 启动后炎症性 CNS 疾病的风险，并评估不同类型潜在自身免疫性疾病或 TNF 抑制剂之间的风险差异。数据来源从建库到 2024 年 3 月 1 日，在 PubMed、Embase 和 Cochrane Library 中进行了单独检索。资料提取和综合研究合格性评估和数据提取由 2 名研究人员按照 PRISMA 指南独立进行。风险比 （RR） 用作汇总分析的效果测量。主要结局和指标主要结局是自身免疫性疾病抗 TNF 治疗后发生炎症性 CNS 事件的风险。根据不同类型的潜在自身免疫性疾病和 TNF 抑制剂进行二次分析。结果分析了 18 项研究，涉及 1 118 428 例自身免疫性疾病患者，随访时间超过 5 698 532 人年。开始使用 TNF 抑制剂后新发炎症性 CNS 事件的发生率为 2.0 至 13.4/10 000 人年。总体而言，与常规疗法相比，暴露于 TNF 抑制剂与任何炎症性 CNS 疾病的风险增加 36% 相关 （RR， 1.36;95% CI， 1.01-1.84;I2,49%），主要归因于脱髓鞘疾病 （RR， 1.38;95% CI， 1.04-1.81;I2,31%）。二次分析显示，不同类型的潜在自身免疫性疾病发生炎症性 CNS 疾病的风险相似（风湿性疾病：RR，1.36;95% CI，0.84-2.21;炎症性肠病 1.49;95% CI，0.93-2.40;亚组的 P = .74）和 TNF 抑制剂（抗 TNF 单克隆抗体与依那西普：RR，1.04;95% CI，0.93-1.15;I2， 0%）。结论和相关性与常规疗法相比，无论背景自身免疫性疾病或 TNF 抑制剂类型如何，暴露于 TNF 抑制剂都与炎症性 CNS 疾病的风险增加 36% 相关。