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Upadacitinib Versus Tofacitinib in Anti-MDA5-Positive Dermatomyositis With Interstitial Lung Disease: A Multi-Centre
Can Xia1, Wanlong Wu1, Saisai Lu2
1Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background And Objective:
The treatment of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease (MDA5+DM-ILD) remains a significant clinical challenge. To compare the effectiveness and safety of upadacitinib (UPA) versus tofacitinib (TOFA) upon 6-month lung transplantation-free survival in newly diagnosed MDA5+DM-ILD patients.
Methods:
This multi-centre cohort study in China enrolled MDA5+DM-ILD patients treated from January 2020 to February 2025. Prevalent/incident new users and non-inferior design along with inverse probability treatment weighting (IPTW) were implemented to emulate randomized controlled trial.
Results:
In the eligible cohort, a total of 106 patients were treated with UPA and 328 with TOFA. The crude 6-month lung transplantation-free survival rates were 71.7% (76/106) in the UPA group and 67.4% (221/328) in the TOFA group. In the IPTW-adjusted cohort, UPA showed a trend toward higher survival than TOFA (p = 0.067), with a weighted risk difference of 10.3% (95% confidence interval -0.4% to 20.2%) meeting the non-inferiority margin (non-inferiority p = 0.003). Sensitivity and subgroup analyses showed consistent results, with potentially greater benefit of UPA in incident JAK inhibitor users (as first-line treatment), monotherapy recipients (without combination with other immunosuppressants except steroid), and those with rapidly progressive ILD. Safety profiles were comparable between groups.
Conclusion:
UPA was found to be non-inferior to TOFA in improving 6-month lung transplantation-free survival among patients with MDA5+DM-ILD, with comparable safety.
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