Objective To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. MethodsWe conducted a multicentre, international, retrospective cohort study. Results149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. ConclusionThe clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

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The idiopathic inflammatory myopathies are chronic diseases of the skeletal muscle that comprise various conditions, including dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and the antisynthetase syndrome. Although there are a number of distinguishing features, all these disorders are characterized by an immune and inflammatory response mainly directed against the muscle. Hence, therapy is geared toward curbing the autoimmune and inflammatory response. A quite wide range of medications are currently available to treat these disorders, but despite all therapeutic progress still a number of patients are unable to maintain a sustained remission. In this review article, we have marshaled a variety of potential therapeutic agents that may hold promise for the future treatment of the idiopathic inflammatory myopathies. It is to be expected that by increasing the therapeutic armamentarium with agents that have different mechanisms of action even challenging cases could be successfully managed, thus reducing disease burden and disability.