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

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.

Overview of the study. ILD: interstitial lung disease; MDA5: melanoma differentiation-associated gene 5; HRCT: high-resolution computed tomography; TOF: tofacitinib; CNI: calcineurin inhibitors; P_aO2: arterial oxygen tension; F_IO2: inspiratory oxygen fraction; IPTW: inverse probability of treatment weighting.

FIGURE 1

Study cohort. MDA5: melanoma differentiation-associated gene 5; ILD: interstitial lung disease.

FIGURE 2

Inverse probability of treatment-weighted lung transplantation-free survival curves among anti-melanoma differentiation-associated gene 5-positive dermatomyositis with interstitial lung disease patients treated with tofacitinib or calcineurin inhibitors. Patients treated with tofacitinib had significantly better lung transplantation-free survival than those treated with calcineurin inhibitors (p=0.013 by the log-rank test).

FIGURE 3

Subgroup analyses. Subgroup analyses show the associations between tofacitinib and the end-point event (all-cause death or lung transplantation within 1 year) according to age (<60 years versus ≥60 years), sex (female versus male), course of interstitial lung disease (ILD) (≤1 month versus >1 month), rapidly progressive ILD (RPILD) or not, forced vital capacity (FVC) ≥50% predicted or not, arterial oxygen tension (P_aO2)/inspiratory oxygen fraction (F_IO2) (≥300 mmHg versus <300 mmHg) and combined immunosuppressants or biologics (no versus yes). Diamonds represent point estimates for the hazard ratio as compared with calcineurin inhibitors, and horizontal lines indicate the associated 95% confidence intervals. p-values for interaction were calculated to evaluate whether treatment effect differs on the survival within subgroups. PFTs: pulmonary function tests; CNI: calcineurin inhibitors.