A Retrospective Study Comparing The Effect Of Tofacitinib And Tacrolimus On Survival In Patients With Anti-Melanoma Differentiation–Associated Gene 5 Antibody-Related Interstitial Lung Disease

ObjectivesAnti-melanoma differentiation-associated gene 5(MDA5)antibody was closely associated with dermatomyositis related interstitial lung disease(DM-ILD),especially rapidly progressive ILD(RPILD).This is a life-threatening phenotype with a high mortality rate for its resistance to conventional therapy.The efficacy of tofacitinib in early diagnosis of MDA5 related ILD(MDA5-ILD)has been described.But whether tofacitinib exposure is associated with a reduced one-year mortality remains undetermined.MethodsPatients diagnosed as MDA5-ILD receiving tofacitinib or tacrolimus treatment in Nanjing University medical school affiliated Drum Tower Hospital from October 2017 to December 2020 were included.The baseline laboratory findings,pulmonary function testing parameters(PFTs),chest high-resolution computed tomography(HRCT)images and treatment information were compared between two groups.Clinical outcomes were 6-month and 1-year mortality rates.The Kaplan–Meier curve with log rank test was used to access differences in survival.Cox proportional hazards model adjusted for age,sex,smoking history,anti-MDA5 antibody titers,concurrent use of other steroids sparing agents was performed to assess the relationship between tofacitinib use and outcomes.ResultsDuring the study period,a total of 61 MDA5-ILD patients were enrolled.Among them,26 patients were treated with tofacitinib and 35 with tacrolimus.The 6-month and 1-year mortality in tofacitinib group were significantly lower than those in tacrolimus group(38.5% vs.62.9%,p=0.028;44.0% vs.65.7%,P=0.031,respectively).The adjusted model showed tofacitinib exposure was associated with a lower risk for 1-year mortality(HR0.438,95%CI 0.200-0.960,P=0.039).While the incidence of adverse events and medication discontinuation rates between the two groups were similar(adverse events: 73.1% and 74.3%,p=1.000;medication discontinuation rates: 23.1% and 14.3%,P=0.504).There were13 patients diagnosed as rapidly progressive-ILD(RPILD)in tofacitinib group and 22 in tacrolimus group.The majority of death occurred in patients with RPILD in both group.The 6-month and 1-year mortality of patients with RPILD in tofacitinib group were also lower than those in tacrolimus group(76.9% and95.5%,p=0.021;84.6% and 100.0%,P=0.017).After adjusted confounding factors,it also showed that tofacitinib use was associated with a lower risk for 1-year mortality in RPILD patients(HR 0.248,95% CI 0.068-0.905,P=0.035).ConclusionsOur observational study showed tofacitinib use might have a potential impact on improving the outcomes of MDA5-ILD without increasing the risk of adverse events.Future clinical trials are needed to assess the long term efficacy and tolerability of tofacitinib.