Efficacy and safety of a triple combination of glucocorticoids, tofacitinib and calcineurin inhibitors in anti-MDA5 positive dermatomyositis

Objectives. To explore the risk factors of early death in dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 (anti-MDA5) antibody (anti-MDA5-DM). To determine the optimal initial treatment regimen for patients with anti-MDA5-DM.Methods. Patients with newly onset anti-MDA5-DM from June 2018 to October 2021 in our center were retrospectively reviewed for 6 months. Patients were divided into five groups based on initial treatments. The major outcome was mortality in 6 months. Secondary outcomes included changing therapy, low-dose-glucocorticoid maintenance, remission and severe infection.Results. A total of 214 patients were included in the study. Five patients (2.34%) were lost to follow-up during 6 months, 63 patients (30.14%) died, 52 patients (24.88%) experienced serious infection, 112 patients (53.59%) achieved remission, and 86 patients (41.15%) were maintained with low-dose glucocorticoids. Age over 50 years, skin ulcer, lactate dehydrogenase (LDH) > 350 U/L, C reactive protein (CRP) > 5mg/L, anti-Ro52 antibody, higher ground-glass opacity (GGO) score, and pulse glucocorticoid at baseline were independent risk factors of mortality in the first 6 months of disease courses. Conversely, arthritis and prophylactic use of compound sulfamethoxazole (SMZ Co) were independent protective factors. Patients initially treated with a triple combination of high-dose glucocorticoid (GC), tofacitinib and high-dose calcineurin inhibitors (CNIs) had the lowest risk of mortality within 6 months, and were more likely to achieve remission under the maintenance of low-dose-glucocorticoids.Conclusion. A triple combination of high-dose GC, tofacitinib and high-dose CNIs is an effective and safe treatment regimen for newly onset anti-MDA5-DM.