Abstract Objective Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5-DM) is often complicated by rapidly progressive interstitial lung disease (RP-ILD), leading to poor prognosis. Although early multidisciplinary therapy has improved survival, most studies have focused on short-term outcomes, and data on long-term prognosis remain limited. Compared with antisynthetase syndrome-associated dermatomyositis (ARS-DM), MDA5-DM has a lower relapse rate; however, a Japanese cohort reported a 5-year relapse-free survival of 77.4%, with approximately 20% experiencing relapse. We aimed to identify predictors of ILD exacerbation during induction therapy in patients with MDA5-DM. Methods We retrospectively reviewed patients with MDA5-DM complicated by ILD who were treated at Kumamoto University Hospital between January 2009 and October 2025. Patients who did not respond to initial therapy and died, or whose post-treatment course could not be followed, were excluded. ILD exacerbation during induction therapy was defined as cases in which pulmonary shadows or respiratory status initially improved with induction therapy but subsequently worsened in respiratory status, imaging, or pulmonary function during steroid tapering, requiring treatment intensification. We compared those who experienced ILD exacerbation during induction therapy with those who did not. Results A total of 24 patients were included: 9 with ILD exacerbation and 15 without. Patients with exacerbation were less likely to have received initial triple therapy (glucocorticoid, calcineurin inhibitor, and intravenous cyclophosphamide IVCY) and ≥3 courses of IVCY compared with the non-exacerbation group. Persistent grade ≥2 transaminase elevation and/or re-elevation after normalization were significantly more common in the exacerbation group. Seroconversion to anti-MDA5 antibody negativity occurred in 3 patients (33.3%) in the exacerbation group versus 11 (73.3%) in the non-exacerbation group. Notably, none of the exacerbation cases had achieved antibody negativity before the event; all three seroconverted only after treatment intensification. All patients with exacerbation improved after therapeutic modification or plasma exchange. Conclusion ILD exacerbation can occur during induction therapy in MDA5-DM, necessitating careful monitoring. In this cohort, patients with exacerbation were less likely to have received initial triple therapy, suggesting that disease severity or treatment intensity at baseline may influence outcomes. Persistent grade ≥2 or recurrent re-elevation of transaminase levels may indicate risk for exacerbation. Failure to achieve seroconversion to anti-MDA5 antibody negativity may indicate a risk of exacerbation during steroid tapering, underscoring the importance of close monitoring. This abstract is funded by: None
Okabayashi et al. (Fri,) studied this question.