Seoul National University Bundang Hospital, Seongnam, South Korea.
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Arthritis Care Res (Hoboken). 2020 Oct;72(10):1383-1391. doi: 10.1002/acr.24038.
To compare the risk of serious infections between the use of tumor necrosis factor inhibitors (TNFi) plus methotrexate (MTX) versus triple therapy among rheumatoid arthritis (RA) patients in a real-world setting.
Using claims data from Truven MarketScan (2003-2014), we conducted a cohort study to compare RA patients receiving MTX who added a TNFi (TNFi plus MTX group) versus MTX plus hydroxychloroquine and sulfasalazine (triple therapy group). The primary outcome was any serious infection (i.e., a composite end point of hospitalized bacterial and opportunistic infections or herpes zoster). Secondary outcomes were individual components of the composite end point. To adjust for baseline confounding, we used propensity score (PS)-based fine stratification and weighting. A weighted Cox proportional hazards model estimated the hazard ratio (HR) and 95% confidence interval (95% CI) of the outcomes.
After PS stratification (PSS) and weighting, we included a total of 45,208 TNFi plus MTX initiators and 1,387 triple therapy initiators. Mean age was 53 years and 70% were female. The incidence rate of any serious infection per 100 person-years was 2.46 in the TNFi plus MTX group and 2.03 in the triple therapy group. The PSS-weighted HR for any serious infection comparing TNFi plus MTX versus triple therapy was 1.23 (95% CI 0.87-1.74). For the secondary outcomes, the PSS-weighted HR was 1.41 (95% CI 0.85-2.34) for bacterial infection and 0.80 (95% CI 0.55-1.18) for herpes zoster.
In this real-world cohort of RA patients, we noted no substantially different risk of any serious infection, bacterial infection, or herpes zoster after initiating TNFi plus MTX versus triple therapy, although CIs were wide.
在真实环境中比较类风湿关节炎（RA）患者使用肿瘤坏死因子抑制剂（TNFi）联合甲氨蝶呤（MTX）与三联疗法治疗时严重感染的风险。
利用 Truven MarketScan（2003-2014 年）的理赔数据，我们进行了一项队列研究，比较了接受 MTX 并加用 TNFi（TNFi 联合 MTX 组）的 RA 患者与 MTX 联合羟氯喹和柳氮磺胺吡啶（三联疗法组）。主要结局为任何严重感染（即住院细菌感染和机会性感染或带状疱疹的复合终点）。次要结局为复合终点的各个组成部分。为了调整基线混杂因素，我们使用倾向评分（PS）进行精细分层和加权。加权 Cox 比例风险模型估计了结局的风险比（HR）和 95%置信区间（95%CI）。
经过 PS 分层（PSS）和加权后，我们纳入了共 45208 例 TNFi 联合 MTX 起始治疗者和 1387 例三联疗法起始治疗者。平均年龄为 53 岁，70%为女性。TNFi 联合 MTX 组和三联疗法组每 100 人年的任何严重感染发生率分别为 2.46 和 2.03。比较 TNFi 联合 MTX 与三联疗法治疗的任何严重感染的 PSS 加权 HR 为 1.23（95%CI 0.87-1.74）。对于次要结局，PSS 加权 HR 分别为细菌感染 1.41（95%CI 0.85-2.34）和带状疱疹 0.80（95%CI 0.55-1.18）。
在这项 RA 患者的真实世界队列中，与三联疗法相比，我们没有观察到起始 TNFi 联合 MTX 治疗后严重感染、细菌感染或带状疱疹的风险有显著差异，尽管置信区间较宽。
