Effectiveness and safety of tofacitinib calcineurin inhibitor in interstitial lung disease secondary to anti-MDA5-positive dermatomyositis: a multi-centre cohort study.

Objective: To compare the effectiveness and safety of tofacitinib (TOF) 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 for this retrospective cohort study. The primary effectiveness endpoint 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 TOF 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 TOF group compared to the CNI group (log-rank p=0.013). Multivariable Cox analysis performed in the IPTW dataset revealed the hazard ratio of TOF CNI for 1-year survival was 0.72 (95% CI, 0.56 to 0.94, p=0.013). The adjusted difference of survival rate was 9.3% (95%CI 2.8% to 15.8%). Alternative analytic strategies yielded consistent results in sensitivity analyses. Patients less than 60 years old, without RPILD, or with baseline PaO/FiO ≥300 mmHg might benefit more from TOF. Opportunistic infection was the major treatment-related serious adverse event, with generally comparable incidence (42.4% 45.3%).

Conclusion: In this large multi-centre cohort study, tofacitinib showed significantly more benefits for 1-year lung transplantation-free survival than calcineurin inhibitors in MDA5+DM-ILD.