Pharmacologic Treatment of Anti-MDA5 Rapidly Progressive Interstitial Lung Disease

Abstract

Purpose of the Review Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders. The presence of different autoantibodies allows clinicians to define distinct phenotypes. Antibodies against the melanoma differentiation-associated protein 5 gene, also called anti-MDA5 antibodies, are associated with a characteristic phenotype, the clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease. This review aims to analyze the different pharmacological options for the treatment of rapidly progressive interstitial lung disease in patients with anti-MDA5 antibodies. Recent Findings Evidence-based therapeutic recommendations suggest that the best initial approach to treat these patients is an early combination of immunosuppressive drugs including either glucocorticoids and calcineurin inhibitors or a triple therapy adding intravenous cyclophosphamide. Tofacitinib, a Janus kinase inhibitor, could be useful according to recent reports. High ferritin plasma levels, generalized worsening of pulmonary infiltrates, and ground-glass opacities should be considered predictive factors of a bad outcome. In this scenario, clinicians should consider rescue therapies such as therapeutic plasma exchange, polymyxin-B hemoperfusion, veno-venous extracorporeal membrane oxygenation, or even lung transplantation. Summary Combined immunosuppressive treatment should be considered the first-line therapy for patients with anti-MDA5 rapidly progressive interstitial lung disease. Aggressive rescue therapies may be useful in refractory patients.

Anti-MDA5 Associated Clinically Amyopathic Dermatomyositis With Rapidly Progressive Interstitial Lung Disease

“…A retrospective study in Japan reproduced these results; however, they reported frequent cytomegalovirus reactivation secondary to severe immunosuppression [13]. For patients unable to tolerate calcineurin inhibitors, mycophenolate mofetil and biological therapies may be considered [11].…”

“…Aggressive and early treatment with the use of multiple immunosuppressive agents is essential in the management of CADM-ILD. First line therapy involves high-dose glucocorticoids combined with calcineurin inhibitors, with or without cyclophosphamide [11]. A multicenter prospective study in Japan found that patients treated initially with a combination of high-dose glucocorticoids, calcineurin inhibitors, and cyclophosphamide had a 6-month survival rate of 89%, compared to 33% in patients treated with a step-up strategy starting with high-dose glucocorticoids [12].…”

“…Refractory disease is defined as lack of clinical response to combined immunosuppression, including glucocorticoids, after 1 week of therapy [11]. Therapeutic options for these patients include addition of a third immunosuppressant (if only on dual therapy) or using a different combination of immunotherapy [11].…”

“…Refractory disease is defined as lack of clinical response to combined immunosuppression, including glucocorticoids, after 1 week of therapy [11]. Therapeutic options for these patients include addition of a third immunosuppressant (if only on dual therapy) or using a different combination of immunotherapy [11]. Nonpharmacological rescue therapies in critically ill patients include plasmapheresis, intravenous immunoglobulin, venovenous extracorporeal membrane oxygenation, and lung transplantation [11].…”

Therapeutic Potential of Janus Kinase Inhibitors for the Management of Interstitial Lung Disease

“… 1 However, occasionally the disease is refractory, rapidly progressive, and resistant to hormonal and immunosuppressive therapies. 15 As a result, it is necessary to develop alternative drug therapies based on the current understanding of ILD pathogenesis and the role of the JAK/STAT pathway in it. The existing knowledge and scientific rationale on the efficacy of JAK inhibitors (JAKi) suggest that they may provide clinicians with a more precise treatment strategy for reducing interstitial inflammation thereby preventing the progression of fibrosis and the continuous deterioration of lung function.…”