Management of Myositis-Associated Interstitial Lung Disease

Idiopathic inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), and clinically amyopathic DM (CADM), are a diverse group of autoimmune diseases characterized by muscular involvement and extramuscular manifestations. Interstitial lung disease (ILD) has major pulmonary involvement and is associated with increased mortality in PM/DM/CADM. The management of PM-/DM-/CADM-associated ILD (PM/DM/CADM-ILD) requires careful evaluation of the disease severity and clinical subtype, including the ILD forms (acute/subacute or chronic), because of the substantial heterogeneity of their clinical courses. Recent studies have highlighted the importance of myositis-specific autoantibodies' status, especially anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl tRNA synthetase (ARS) antibodies, in order to evaluate the clinical phenotypes and treatment of choice for PM/DM/CADM-ILD. Because the presence of the anti-MDA5 antibody is a strong predictor of a worse prognosis, combination treatment with glucocorticoids (GCs) and calcineurin inhibitors (CNIs; tacrolimus (TAC) or cyclosporin A (CsA)) is recommended for patients with anti-MDA5 antibody-positive DM/CADM-ILD. Rapidly progressive DM/CADM-ILD with the anti-MDA5 antibody is the most intractable condition, which requires immediate combined immunosuppressive therapy with GCs, CNIs, and intravenous cyclophosphamide. Additional salvage therapies (rituximab, tofacitinib, and plasma exchange) should be considered for patients with refractory ILD. Patients with anti-ARS antibody-positive ILD respond better to GC treatment, but with frequent recurrence; thus, GCs plus immunosuppressants (TAC, CsA, azathioprine, and mycophenolate mofetil) are often needed in order to achieve favorable long-term disease control. PM/DM/CADM-ILD management is still a therapeutic challenge for clinicians, as evidence-based guidelines do not exist to help with management decisions. A few prospective clinical trials have been recently reported regarding the treatment of PM/DM/CADM-ILD. Here, the current knowledge on the pharmacologic managements of PM/DM/CADM-ILD was mainly reviewed.