Pretreatment Cytokine Signatures as Candidate Biomarkers for JAK Inhibitor Response in Anti-MDA5 Dermatomyositis-Related Interstitial Lung Disease: A Pilot Study

抗MDA5皮肌炎相关间质性肺病JAK抑制剂疗效的候选生物标志物:预处理细胞因子特征的初步研究

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Abstract

OBJECTIVE: To evaluate the clinical characteristics and serum cytokine profiles of patients with anti-MDA5 antibody-positive dermatomyositis with interstitial lung disease (MDA5+ DM-ILD) treated with JAK inhibitors and to compare survivors and nonsurvivors. METHODS: Six patients diagnosed with MDA5+ DM-ILD at Nagasaki University Hospital (from 2018 to 2023) were analyzed. All patients received high-dose glucocorticoids, intravenous cyclophosphamide, and plasma exchange. Five patients received calcineurin inhibitors. JAK inhibitors (tofacitinib, n = 3; baricitinib, n = 3) were added to the treatment regimen. Clinical data, including serum ferritin levels, hypoxemia status, and lymphocyte counts, were recorded at initial presentation and during JAK inhibitor treatment. Serum cytokine levels were analyzed using multiplex assays. RESULTS: The mean patient age was 66.6 years, and four patients were women. Three patients died within six months of starting JAK inhibitor therapy. Nonsurvivors had higher initial ferritin levels than survivors (mean 3,413 vs 809 ng/mL). Hypoxemia was present in five patients at JAK inhibitor initiation, and four patients had low lymphocyte counts. Serum cytokine analysis revealed elevated levels of granulocyte colony-stimulating factor, interferon-α, interleukin-4, interleukin-13, and CXCL8 in nonsurvivors compared with survivors. CONCLUSIONS: Serum cytokine profiles may serve as prognostic markers in patients with MDA5+ DM-ILD treated with JAK inhibitors. The persistent elevation of multiple cytokines in nonsurvivors may reflect inadequate suppression of the cytokine storm despite treatment. Further research is needed to determine the optimal selection and timing of JAK inhibitor therapy.

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