Wu Wanlong, Guo Bingpeng, Sun Wenjia, Chen Dan, Xu Wenwen, Chen Zhiwei, Fu Yakai, Ye Yan, Lyu Xia, Xue Zhixin, Wang Kaiwen, Zhao Jiangfeng, Xie Cuiying, Chen Yi, Ye Chunhua, Dai Min, Fan Wei, Li Jia, Wang Xiaodong, Xue Yu, Wan Weiguo, Sun Li, Wu Huaxiang, Luo Qun, Han Qian, Fu Qiong, Ye Shuang
Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
State Key Laboratory of Respiratory Disease, National Clinical Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Eur Respir J. 2025 May 22;65(5). doi: 10.1183/13993003.01488-2024. Print 2025 May.
To compare the effectiveness and safety of tofacitinib calcineurin inhibitor (CNI) as initial immunosuppressive regimen for anti-melanoma differentiation-associated gene 5-positive dermatomyositis with interstitial lung disease (MDA5DM-ILD).
Adult Chinese patients with newly diagnosed MDA5DM-ILD (ILD course <3 months) from five tertiary referral centres between April 2014 and January 2023 were included in this retrospective cohort study. The primary effectiveness end-point was lung transplantation-free survival within 1 year. Propensity score-based inverse probability of treatment weighting (IPTW) was applied for adjustment in this real-world study.
In the eligible cohort, a total of 94 (32.4%) and 105 (46.7%) patients died or underwent lung transplantation within 1 year in the tofacitinib group (n=290) and the CNI group (n=225), respectively. After adjustment by IPTW, patients' lung transplantation-free survival rate within 1 year was significantly higher in the tofacitinib group compared to the CNI group (log-rank p=0.013). Multivariable Cox analysis performed in the IPTW dataset revealed that the hazard ratio of tofacitinib CNI for 1-year survival was 0.72 (95% CI 0.56-0.94; p=0.013). The adjusted difference of survival rate was 9.3% (95% CI 2.8-15.8%). Alternative analytic strategies yielded consistent results in sensitivity analyses. Patients aged <60 years, without rapidly progressive ILD, or with baseline arterial oxygen tension/inspiratory oxygen fraction ≥300 mmHg might benefit more from tofacitinib. Opportunistic infection was the major treatment-related serious adverse event, with generally comparable incidence (42.4% 45.3%).
In this large multicentre cohort study, tofacitinib showed significantly more benefits for 1-year lung transplantation-free survival than calcineurin inhibitors in MDA5DM-ILD.
比较托法替布与钙调神经磷酸酶抑制剂（CNI）作为抗黑色素瘤分化相关基因5阳性皮肌炎伴间质性肺病（MDA5DM-ILD）初始免疫抑制方案的有效性和安全性。
本回顾性队列研究纳入了2014年4月至2023年1月期间来自五个三级转诊中心的新诊断为MDA5DM-ILD（ILD病程<3个月）的成年中国患者。主要有效性终点是1年内无肺移植生存。在这项真实世界研究中，采用基于倾向评分的治疗加权逆概率（IPTW）进行调整。
在符合条件的队列中，托法替布组（n=290）和CNI组（n=225）分别有94例（32.4%）和105例（46.7%）患者在1年内死亡或接受肺移植。经IPTW调整后，托法替布组患者1年内无肺移植生存率显著高于CNI组（对数秩检验p=0.013）。在IPTW数据集中进行的多变量Cox分析显示，托法替布对比CNI的1年生存风险比为0.72（95%CI 0.56-0.94；p=0.013）。生存率的调整差异为9.3%（95%CI 2.8-15.8%）。替代分析策略在敏感性分析中产生了一致的结果。年龄<60岁、无快速进展性ILD或基线动脉血氧张力/吸入氧分数≥300 mmHg的患者可能从托法替布中获益更多。机会性感染是主要的治疗相关严重不良事件，发生率总体相当（42.4%对45.3%）。
在这项大型多中心队列研究中，托法替布在MDA5DM-ILD中1年无肺移植生存方面显示出比钙调神经磷酸酶抑制剂显著更多的益处。
