Difficult-to-treat rheumatoid arthritis: systematic review and meta-analysis on global prevalence.

This study aimed to systematically evaluate the global prevalenceof D2T-RA using the European League Against Rheumatism (EULAR) definition and to quantify the proportion attributable to persistent inflammatory refractory rheumatoid arthritis (RA).

本研究旨在系统评估使用欧洲抗风湿病联盟（EULAR）定义的难治性类风湿关节炎（D2T-RA）的全球患病率，并量化持续性炎症性难治性类风湿关节炎（RA）所占的比例。

Methods

We comprehensively searched PubMed, EMBASE, and Cochrane Library (up to April 2025) for observational studies reporting the prevalenceof D2T-RA according to the EULAR definition.

我们全面检索了PubMed、EMBASE和Cochrane图书馆（截至2025年4月），寻找根据EULAR定义报告D2T-RA患病率的观察性研究。

Subgroup analyses were performed to explore heterogeneity sources.

进行了亚组分析以探索异质性的来源。

Random-effects meta-analysisof proportions using generalised linear mixed models was conducted to calculate pooled prevalencerates and 95% CI.

采用广义线性混合模型进行随机效应比例元分析，以计算汇总的患病率及其95%置信区间。

Results

Twenty-three studies with 27,987 patients with RA from 13 countries were included.

纳入了来自13个国家的23项研究，共有27,987名类风湿关节炎患者。

The global pooled prevalenceof D2T-RA was 11.7% (95% CI: 9.5%-14.3%).

D2T-RA的全球汇总患病率为11.7%（95%置信区间：9.5%-14.3%）。

The pooled prevalenceof D2T-RA was 10.9% (95% CI: 8.2%-14.2%) in overall RA cohorts and 13.2% (95% CI: 9.1%-18.8%) in studies restricted to biologic and target synthetic disease-modifying antirheumatic drugs (b/tsDMARDs)-treated populations.

在所有RA队列中，D2T-RA的汇总患病率为10.9%（95%置信区间：8.2%-14.2%），而在仅限于生物制剂和靶向合成疾病修饰性抗风湿药物（b/tsDMARDs）治疗的人群研究中，患病率为13.2%（95%置信区间：9.1%-18.8%）。

D2T-RA prevalencewas stable in the region, RA criteria, and study setting; significant variations only existed in the enrolled period (pre-2020 vs post-2020: 9.86% [95% CI: 7.6%-12.7%] vs 14.3% [95% CI: 10.3%-19.6%]; P = .08).

D2T-RA的患病率在该地区、RA诊断标准和研究设置中保持稳定；只有在纳入研究的时期（2020年前后）存在显著差异（2020年前：9.86% [95% 置信区间: 7.6%-12.7%]；2020年后：14.3% [95% 置信区间: 10.3%-19.6%]；P = .08）。

Moreover, about half of patients with D2T-RA exhibited evidence of persistent inflammatory refractory RA (pooled proportion: 47.1%, 95% CI: 33.3%-61.4%).

此外，大约一半的D2T-RA患者表现出持续性炎症难治性RA的证据（汇总比例：47.1%，95% 置信区间: 33.3%-61.4%）。

Prevalencedecreased sharply with stricter definitions: D2T(3)-RA (≥3 b/tsDMARD failures): 4.3% (2.7%-6.7%) and D2T(4)-RA (≥4 failures: 1.6% (0.6%-4.3%).

随着定义的严格化，患病率急剧下降：D2T(3)-RA（≥3次b/tsDMARD治疗失败）：4.3%（2.7%-6.7%），D2T(4)-RA（≥4次失败）：1.6%（0.6%-4.3%）。

Conclusions

Based on available global data, approximately 12% of patients with RA meet standard D2T-RA criteria, with nearly half exhibiting persistent inflammatory disease.

根据现有的全球数据，大约12%的类风湿关节炎患者符合标准的D2T-RA标准，其中近一半患者表现出持续的炎症性疾病。

Stricter definitions with failure of ≥3 b/tsDMARD identify the small group of patients for whom innovative treatments or strategies are needed.

更严格的定义，即在≥3种b/tsDMARD治疗失败后，可以识别出需要创新治疗或策略的小群体患者。