Effectiveness and safety of tofacitinib<i>versus</i>calcineurin inhibitor in interstitial lung disease secondary to anti-MDA5-positive dermatomyositis: a multicentre cohort study
Wanlong Wu, Bingpeng Guo, Wenjia Sun, Dan Chen, Wenwen Xu, Zhiwei Chen, Yakai Fu, Yan Ye, X. Lyu, Zhixin Xue, Kaiwen Wang, Jiangfeng Zhao, Cuiying Xie, Yi Chen, Chunhua Ye, Min Dai, Wei Fan, Jia Li, Xiaodong Wang, Yu Xue, Weiguo Wan, Li Sun, Huaxiang Wu, Qun Luo, Qian Han, Qiong Fu, Shuang Ye
Abstract
Objective To compare the effectiveness and safety of tofacitinib versus calcineurin inhibitor (CNI) as initial immunosuppressive regimen for anti-melanoma differentiation-associated gene 5-positive dermatomyositis with interstitial lung disease (MDA5 + DM-ILD). Methods Adult Chinese patients with newly diagnosed MDA5 + DM-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. Results 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 versus 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% versus 45.3%). Conclusion In this large multicentre cohort study, tofacitinib showed significantly more benefits for 1-year lung transplantation-free survival than calcineurin inhibitors in MDA5 + DM-ILD.