Efficacy of plasma exchange in anti-MDA5-positive dermatomyositis with interstitial lung disease under combined immunosuppressive treatment

• Published in: Rheumatology (Oxford, England) England), 2020-11, Vol.59 (11), p.3284-3292
• Main Authors: Shirakashi, Mirei, Nakashima, Ran, Tsuji, Hideaki, Tanizawa, Kiminobu, Handa, Tomohiro, Hosono, Yuji, Akizuki, Shuji, Murakami, Kosaku, Hashimoto, Motomu, Yoshifuji, Hajime, Ohmura, Koichiro, Mimori, Tsuneyo
• Format: Article
• Language: English
• Subjects: Adult; Antigens, CD - blood; Antigens, Differentiation, Myelomonocytic - blood; Autoantibodies - blood; Cyclosporine - therapeutic use; Dermatomyositis - blood; Dermatomyositis - mortality; Dermatomyositis - therapy; Drug Resistance; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents - therapeutic use; Interferon-Induced Helicase, IFIH1 - immunology; Interferons - blood; Interleukins - blood; Japan; Lung Diseases, Interstitial - blood; Lung Diseases, Interstitial - mortality; Lung Diseases, Interstitial - therapy; Male; Middle Aged; Plasma Exchange; Receptors, Cell Surface - blood; Tacrolimus - therapeutic use
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/keaa123

Rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis often accompanies anti-melanoma differentiation-associated gene 5 (MDA5)-positive DM. Combined immunosuppressive therapy, including glucocorticoids, calcineurin inhibitors and intravenous cyclophosphamide (IVCY) is reportedly effective in DM with RP-ILD, but some patients remain resistant to therapy. We examined the utility of plasma exchange (PE) in such intractable cases and investigated the prognostic factors of the disease. Thirty-eight anti-MDA5-positive DM-ILD patients who received the combined immunosuppressive therapy were retrospectively reviewed. Their serum cytokines were evaluated by multiplex assay before treatment. The patients were divided into two groups: those who achieved remission without exacerbation of respiratory dysfunction (n = 25, group A) and those who progressed to hypoxemia during the treatment (n = 13, group B). PE was carried out in eight group B patients, but none of group A. Five of the eight treated with PE survived, while the five untreated patients died (P =0.04). Higher neutrophil lymphocyte ratio, higher serum ferritin, hypoxemia, high-resolution computed tomography (HRCT) score before treatment and increase of Krebs von Lungen-6 (KL-6) in the first 4 weeks of the treatment were the prognostic factors for disease progression. Serum cytokines such as IL-1, IL-6, IL-8, IL-10, IL-12p70, IL-18 and sCD163 levels were higher in group B than group A. PE should be an effective adjuvant treatment in anti-MDA5-positive DM with RP-ILD. Assessment of basal laboratory tests or monocyte/macrophage-derived cytokines and the increase of KL-6, HRCT score and hypoxemia may help us to predict intractable cases and to make early treatment decisions regarding PE in anti-MDA5-positive DM.