ORIGINAL ARTICLE Combined immunosuppressive therapy provides favorable prognosis and increased risk of cytomegalovirus reactivation in anti-melanoma differentiation-associated gene 5 antibody- positive dermatomyositis Kazuki M. MATSUDA, Ayumi YOSHIZAKI, Ai KUZUMI, Takemichi FUKASAWA, Satoshi EBATA, Asako YOSHIZAKI-OGAWA, Shinichi SATO Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan ABSTRACT Anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) is myositis-specific autoantibody associ- ated with rapidly progressive interstitial lung disease (ILD) and poor prognosis. In this retrospective observational study, we aimed to verify the efficacy and safety of introducing combined immunosuppressive therapy for anti- MDA5 Ab-positive dermatomyositis (DM) from their early stage. We recruited all Japanese patients diagnosed with DM in our clinic between January 2011 and October 2018, who had anti-MDA5 Ab, anti-aminoacyl transfer RNA synthetase Ab or anti-transcriptional intermediary factor 1-c Ab. Combined immunosuppressive therapy was defined as combination of systemic corticosteroids, i.v. cyclophosphamide and tacrolimus. The difference of clini- cal features among the three groups was analyzed by multiple comparison analysis. The longitudinal change of the measurements from baseline was examined by Wilcoxon signed-rank test. Association between therapeutic regimens and adverse events was examined by logistic regression analysis. As a result, combined immunosup- pressive therapy was most frequently used in the anti-MDA5 Ab-positive group, which significantly improved their forced vital capacity of the lung. Interval time since initial visit until starting treatment was the shortest in the anti-MDA5 Ab-positive group. There was no significant difference in the incidence of death and recurrence among the three groups. Cytomegalovirus reactivation was most common in the anti-MDA5 Ab-positive group, associ- ated with combined immunosuppressive therapy. Collectively, early introduction of combined immunosuppressive therapy was effective for DM patients with anti-MDA5 Ab. At the same time, clinicians should be aware of the risk of cytomegalovirus reactivation during the treatment. Key words: anti-melanoma differentiation-associated gene 5 antibody, combined immunosuppressive therapy, cytomegalovirus, dermatomyositis, interstitial lung disease. INTRODUCTION Interstitial lung disease (ILD) is one of the major complica- tions of dermatomyositis (DM), which often determines the mortality of DM patients. 1 In particular, some cases have poor response to treatment and present an extremely unfa- vorable prognosis, which are classified as rapidly progressive ILD (RPILD). 2 Treatment for DM-associated ILD (DM-ILD) is combination of systemic corticosteroids and immunomodula- tors such as i.v. cyclophosphamide (IVCY), tacrolimus (TAC) or i.v. immunoglobulin (IVIG). It is crucial to predict the clini- cal course of DM-ILD, especially identifying DM patients in danger of RPILD, to determine the intensiveness of immuno- suppression. The recent paradigm shift in DM management is the introduction of prognosis prediction from myositis-specific autoantibodies. 3 For instance, DM-ILD associated with the anti-aminoacyl transfer RNA synthetase (ARS) antibody (Ab) shows chronic progression and preferable response to systemic corticosteroids, but is prone to recurrence. 4 The anti- transcriptional intermediary factor 1-c (TIF1-c) Ab is often detected from malignancy-associated DM, which is character- ized by low prevalence of DM-ILD. 5 The anti-melanoma differ- entiation-associated gene 5 (MDA5) Ab has been recently added to the list of myositis-specific autoantibodies. Measure- ment of anti-MDA5 Ab is important because it relates to RPILD and poor prognosis, especially in the Japanese population. 6 Appropriate therapy should be introduced as soon as possible Correspondence: Ayumi Yoshizaki, M.D., Ph.D., Department of Dermatology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Email: ayuyoshi@me.com Received 4 November 2019; accepted 26 January 2020. 1 © 2020 Japanese Dermatological Association doi: 10.1111/1346-8138.15274 Journal of Dermatology 2020; : 1–7