非tnfi生物和靶向合成DMARDs在类风湿关节炎相关间质性肺病中的作用：一项倾向评分匹配、活性比较、新用户研究

IF 4.6 2区医学 Q1 RHEUMATOLOGY

Seminars in arthritis and rheumatism Pub Date : 2025-04-21 DOI:10.1016/j.semarthrit.2025.152735

Halie Frideres , Christopher S. Wichman , Jianghu Dong , Punyasha Roul , Yangyuna Yang , Joshua F. Baker , Michael D. George , Tate M. Johnson , Jorge Rojas , Brian C. Sauer , Grant W. Cannon , Scott M. Matson , Jeffrey R. Curtis , Ted R. Mikuls , Bryant R. England

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引用次数: 0

摘要

目的：本研究旨在使用靶标试验模拟框架比较利妥昔单抗、阿巴接受、托珠单抗和托法替尼启动剂治疗类风湿关节炎相关间质性肺疾病（RA-ILD）的治疗结果。方法我们模拟了三个试验，比较阿巴接受、托珠单抗和托法替尼与利妥昔单抗（参考）。使用2006年至2020年国家退伍军人事务（VA）数据，满足验证的RA-ILD算法启动这些非tnfi b/ tsdmard之一的患者倾向评分（PS）匹配（1:1）。PS模型包括人口统计学、合并症、一般健康状况指标，以及一些与类风湿性关节炎和ild相关的严重程度指标。综合研究结果是死亡和呼吸相关住院，通过VA数据和与国家死亡指数和医疗保险的联系确定，超过三年（主要）和一年的随访期（次要）。采用Cox回归模型对研究结果进行分析，并对不平衡变量进行调整。进行了一些敏感性和亚组分析。结果在初始队列中，我们1:1匹配阿巴接受（n = 150）、托珠单抗（n = 73）和托法替尼（n = 94）与相同数量的利妥昔单抗起始剂（平均年龄68.1-69.4岁，88% - 92%为男性）。两组间的主要综合结局无显著差异(abataccept aHR: 1.03 [0.72, 1.47]；tocilizumab aHR: 1.15 [0.68, 1.93]；tofacitinib aHR: 0.89[0.54, 1.46])。次要、亚组和敏感性分析支持主要发现。结论：我们没有发现RA-ILD患者在死亡率或呼吸系统住院方面存在显著差异，尽管估计不精确，并且可能存在残留的混杂因素。这些发现强调了对RA-ILD进行高级免疫调节疗法的临床试验的必要性。

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Non-TNFi biologic and targeted synthetic DMARDs in rheumatoid arthritis-associated interstitial lung disease: A propensity score-matched, active-comparator, new-user study

Objectives

This study aimed to compare treatment outcomes in rheumatoid arthritis-associated interstitial lung disease (RA-ILD) between initiators of rituximab, abatacept, tocilizumab, and tofacitinib using the Target Trial Emulation Framework.

Methods

We emulated three trials comparing abatacept, tocilizumab, and tofacitinib with rituximab (reference). Patients fulfilling validated RA-ILD algorithms initiating one of these non-TNFi b/tsDMARDs were propensity score (PS)-matched (1:1) using national Veterans Affairs (VA) data from 2006 to 2020. PS models included demographics, comorbidities, general health status indicators, and several RA- and ILD-related severity measures. Composite study outcomes were death and respiratory-related hospitalization, ascertained by VA data and linkages to the National Death Index and Medicare, over three-year (primary) and one-year follow-up periods (secondary). Cox regression models were used to analyze study outcomes adjusting for any unbalanced variables. Several sensitivity and subgroup analyses were performed.

Results

In the primary cohort, we 1:1 matched abatacept (n = 150), tocilizumab (n = 73), and tofacitinib (n = 94) with equal numbers of rituximab initiators (mean age 68.1–69.4 years, 88–92 % male). There were no significant differences in the primary composite outcome among any of the comparisons (abatacept aHR: 1.03 [0.72, 1.47]; tocilizumab aHR: 1.15 [0.68, 1.93]; tofacitinib aHR: 0.89 [0.54, 1.46]). Secondary, subgroup, and sensitivity analyses supported the main findings.

Conclusions

We did not find significant differences in mortality or respiratory hospitalization between RA-ILD patients initiating different non-TNFi b/tsDMARDs, though estimates were imprecise, and residual confounding may be present. These findings emphasize the need for clinical trials of advanced immunomodulatory therapies in RA-ILD.

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来源期刊

Seminars in arthritis and rheumatism 医学-风湿病学

CiteScore

9.20

自引率

4.00%

发文量

176

审稿时长

46 days

期刊介绍： Seminars in Arthritis and Rheumatism provides access to the highest-quality clinical, therapeutic and translational research about arthritis, rheumatology and musculoskeletal disorders that affect the joints and connective tissue. Each bimonthly issue includes articles giving you the latest diagnostic criteria, consensus statements, systematic reviews and meta-analyses as well as clinical and translational research studies. Read this journal for the latest groundbreaking research and to gain insights from scientists and clinicians on the management and treatment of musculoskeletal and autoimmune rheumatologic diseases. The journal is of interest to rheumatologists, orthopedic surgeons, internal medicine physicians, immunologists and specialists in bone and mineral metabolism.