Case Report: Glucocorticoids with Early Aggressive Rituximab and Upadacitinib regimen in the treatment of three patients with anti-MDA5 dermatomyositis-associated interstitial lung disease.

BACKGROUND: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) dermatomyositis (DM) is a severe phenotype that is frequently complicated by rapidly progressive interstitial lung disease (RP-ILD), which carries high mortality despite conventional immunosuppression. Given the dual pathogenesis involving B-cell activation and dysregulated interferon (IFN) pathways, there is a rationale for combining rituximab with Janus kinase (JAK) inhibitors. METHODS: We present three patients with anti-MDA5 DM and severe ILD who were treated at a single center with a novel aggressive triple regimen consisting of high-dose glucocorticoids, rituximab, and upadacitinib. Patients were reviewed for clinical, biochemical, and radiological responses. RESULTS: All three patients demonstrated significant clinical and objective improvement following the initiation of the glucocorticoid-rituximab-upadacitinib regimen, including resolution of skin disease, improvement in lung function and high-resolution computed tomography (HRCT) findings, and reduction in disease activity markers. No deaths were observed during at least 6 month of follow-up. Serious opportunistic infections occurred in one patient. Concomitant intravenous immunoglobulin (IVIG) therapy was administered to one patient with dysphagia and to one patient with superimposed infection. CONCLUSION: An early aggressive regimen of dual-pathway inhibition combining rituximab and upadacitinib, in addition to high-dose glucocorticoids and adjunctive IVIG therapy, may be an effective therapeutic strategy for severe anti-MDA5-associated ILD.