Background:This is an extended report of our study [1]. Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies, which are closely related to interstitial lung disease (ILD) with or without rapid progression, are a type of myositis-specific autoantibody. Since rapid progressive-ILD (RP-ILD) with anti-MDA5 antibodies is refractory and fatal, intensive immunosuppressive therapy with combination calcineurin inhibitor, and intravenous pulse cyclophosphamide was developed, and was shown to improve patient survival and prognosis [2]. However, 20–30% of cases were still fatal, and several additional therapies have been reported e.g. tofacitinib [3] and plasma exchange therapy (PE) [1, 4, 5].Objectives:We evaluated the effect of plasma exchange (PE) on survival in patients with refractory RP-ILD who were positive for anti-MDA5 antibodies.Methods:Among 167 patients newly diagnosed with PM/DM, clinically amyopathic DM, or cancer associated myositis from 2008 to 2019 at our hospital, 12 were diagnosed with refractory RP-ILD and were positive for anti-MDA5 antibodies. PE was used as an adjunct to standard therapy and consisted of fresh frozen plasma as replacement solution. The primary outcome was non-disease-specific mortality. anti-MDA5 antibody titres were measured by ELISA using the MESACUP anti-MDA5 test in 155 patients whose serum was frozen and stored at the time of diagnosis.Results:Anti-MDA5 antibodies were detected in 35 patients, of whom 26 were diagnosed with RP-ILD and 11 were refractory to intensive immunosuppressive therapy. Seven patients received PE (PE group) and four did not (non-PE group). The 1-year survival rate of the PE group was higher than that of the non-PE group (100% and 25%, respectively, P = 0.011). Regarding adverse events associated with PE, two patients had anaphylactic shock, one had high fever due to fresh frozen plasma allergy and one had a catheter infection. All adverse events resolved with appropriate treatment.Conclusion:We evaluated the association between 1-year survival rate and PE for refractory RP-ILD in patients positive for anti-MDA5 antibodies. Intensive immunosuppressive therapy improved the survival rate in RP-ILD patients with anti-MDA5 antibodies, but 20-30% of cases were still fatal. PE could be administered to patients with active infectious disease who were immunocompromised by intensive immunosuppressive therapy. PE may be considered in refractory RP-ILD patients positive for anti-MDA5 antibodies.References:[1]Nakashima R, Hosono Y, Mimori T. Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease. Lupus. 2016;25:925-33.[2]Kurasawa K, Arai S, Namiki Y et al. Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis. Rheumatology. 2018;57:2114-9.[3]Silveira MG, Selva-O’Callaghan A, Ramos-Terrades N et al. Anti-MDA5 dermatomyositis and progressive interstitial pneumonia. QJM. 2016;109:49-50.[4]Endo Y, Koga T, Suzuki T et al. Successful treatment of plasma exchange for rapidly progressive interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis: A case report. Medicine (Baltimore). 2018;97:e0436.[5]Abe Y, Kusaoi M, Tada K et al. Successful treatment of anti-MDA5 antibody-positive refractory interstitial lung disease with plasma exchange therapy. Rheumatology. 2019.Acknowledgments:Funding: This work was supported by Japan Society for the Promotion of Science KAKENHI Grant Number JP18K15433.Disclosure of Interests:None declared
A Case of Clinically Amyopathic Dermatomyositis that was Refractory to Intensive Immunosuppressive Therapy including Tofacitinib, but Successfully Treated with Plasma Exchange Therapy
