Management of MDA-5 antibody positive clinically amyopathic dermatomyositis associated interstitial lung disease: A systematic review.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis (CADM) is frequently associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality rates. There is a lack of data on management of this often fatal condition. The aim of this systematic review was to evaluate current evidence that assesses the available management options and discuss the associated management challenges. This systematic review was conducted according to PRISMA guidelines.  Online databases were searched from inception to April of 2021 using the search terms: "dermatomyositis" OR "amyopathic dermatomyositis" OR "clinically amyopathic dermatomyositis" AND "MDA-5″ OR "melanoma differentiation-associated gene-5″ OR "CADM-140″ AND "management" OR "treatment" OR "therapy" OR "therapeutics". Articles assessing the use of pharmacologic agents on 10 or more patients with MDA5-antibody positive CADM associated with ILD were included. Narrative or systematic reviews and meta-analyses were not eligible for inclusion. A total of 15 eligible studies and 399 unique patients were selected. We identified only one open-label randomized controlled trial (RCT) that examined the management of anti-MDA5 antibody CADM/DM-ILD. Further, 3 cohort studies with prospective arms matched against historical controls, 10 retrospective cohort studies, and 1 retrospective case series were included. A combined therapeutic regimen of high-dose systemic glucocorticoids and other immunosuppressive agents such as calcineurin inhibitors and/or cyclophosphamide, administered early, appears to give the highest rates of survival in those with RP-ILD, while additional therapies such as plasma exchange can be added for refractory disease. Further, tofacitinib and rituximab might have a place in the therapeutic armamentarium of this challenging to treat condition.   Early detection and treatment are of extreme importance, given the risk for rapid decline and high mortality in this subset of patients. There are limited RCTs evaluating the treatment of ILD associated with MDA5-antibody positive CADM. Initiating a combined immunosuppressive therapeutic regimen early in the disease course improves overall morbidity and mortality. RCTs and larger prospective studies are needed to provide high-quality evidence to inform future treatment guidelines.

McPherson M ，Economidou S ，Liampas A ，Zis P ，Parperis K ... -  《-》

Management of Myositis-Associated Interstitial Lung Disease.

Fujisawa T 《-》

Comparison of characteristics and anti-MDA5 antibody distribution and effect between clinically amyopathic dermatomyositis and classic dermatomyositis: a retrospective case-control study.

Ji Q ，Pan W ，Zhang D ，Hou Y ，Wang Z ... -  《Frontiers in Immunology》

A case of anti-MDA5-positive rapidly progressive interstitial lung disease in a patient with clinically amyopathic dermatomyositis ameliorated by rituximab, in addition to standard immunosuppressive treatment.

Koichi Y ，Aya Y ，Megumi U ，Shunichi K ，Masafumi S ，Hiroaki M ，Masahiko K ，Shinsuke K ，Manabu U ，Kenichiro H ，Fumiaki A ，Nozomi A ，Toshitaka M ，Masayoshi Y ，Chikako K ，Yoshinao M ，Tatsuo S ，Masahiko K ... -  《-》

Differential clinical features of patients with clinically amyopathic dermatomyositis who have circulating anti-MDA5 autoantibodies with or without myositis-associated autoantibodies.

Anti-melanoma differentiation-associated gene 5 (MDA5) autoantibodies have been identified as myositis-specific autoantibodies that are often associated with clinically amyopathic dermatomyositis (CADM) and a poor prognosis due to rapidly progressive interstitial lung disease (RP-ILD) in East Asian patients. Besides anti-MDA5 autoantibodies, patients with CADM may have myositis-associated autoantibodies (MAAs), which characterize other connective tissue diseases such as rheumatoid arthritis and Sjögren's syndrome. However, the clinical significance of the coexistence of anti-MDA5 autoantibodies and MAAs in patients with CADM remains unclear. We retrospectively analyzed 24 patients with CADM who had anti-MDA5 autoantibodies. Their clinical phenotypes including laboratory test results, high-resolution lung computed tomography data, response to therapy, and prognosis were compared between those who were positive and negative for MAAs, such as antinuclear antibody (ANA), anti-cyclic citrullinated peptide (CCP), anti-SSA, and anti-SSB antibodies. Among 24 patients, 9 (37.5%) additionally had at least one of the MAAs examined in this study: 1 patient was positive for ANA, 5 for anti-CCP, 5 for either anti-SSA or anti-SSB, 1 for anti-cardiolipin, and 1 for anti-Scl-70. Although all anti-MDA5-positive patients with CADM had ILD, the MAA-positive patients showed a lower risk of developing RP-ILD (p = 0.03), a more favorable response to combination therapy of corticosteroids and immunosuppressive agents, and a lower mortality rate than patients with no MAAs (p = 0.03). Our data suggest that anti-MDA5-positive patients with CADM who also have MAAs have a better prognosis than those without MAAs; thus, anti-MDA5 autoantibodies by themselves may not be strong predictors of worse clinical outcomes in patients with CADM. Coexistent MAAs could be biomarkers for a favorable prognosis in anti-MDA5-positive patients with CADM.

Yamaguchi K ，Yamaguchi A ，Kashiwagi C ，Sawada Y ，Taguchi K ，Umetsu K ，Oshima K ，Uchida M ，Suzuki M ，Kono S ，Takemura M ，Masubuchi H ，Kitahara S ，Hara K ，Maeno T ，Motegi SI ，Muro Y ，Sakairi T ，Hisada T ，Kurabayashi M ... -  《-》