Distinct anti-MDA5 antibody trajectories associated with long-term outcomes in 6-month survivors of anti-MDA5 dermatomyositis with interstitial lung disease

Anti-MDA5 antibody-positive dermatomyositis (DM) is characterized by the presence of anti-MDA5 antibodies. We aimed to assess longitudinal changes of anti-MDA5 antibody levels and long-term outcomes in 6-month survivors of anti-MDA5 + DM with interstitial lung disease (ILD). Anti-MDA5 antibody titers were measured using enzyme-linked immunosorbent assay upon newly diagnosed anti-MDA5 + DM-ILD patients. Patients with follow-up beyond 6 months and at least two anti-MDA5 antibody measurements were subsequently subjected to group-based trajectory analysis by utilizing latent class mixture model. Seroconversion was defined as a change from positive to negative for anti-MDA5 antibodies. Outcome measurements include low disease activity (LDA) status and remission. In 6-month survivors, two anti-MDA5 antibody trajectories were identified: “fast seroconvertors” and “slow seroconvertors”. The median time to anti-MDA5 seroconversion for fast seroconvertors was 9 (IQR: 5–15) months, whereas slow seroconvertors did not achieve 50% anti-MDA5 seroconversion during the follow-up period. Although with a lower baseline PaO 2 /FiO 2 ( P = 0.01), along with a lower baseline anti-MDA5 antibody level ( P < 0.001), these anti-MDA5 fast seroconvertors had a much higher rate of LDA attainment compared to slow seroconvertors at 12 months (66.0% vs. 37.2%, P < 0.001); as well as a greater proportion of prednisone-free remission by 24 months (16.7% vs. 8.8%, P = 0.02), and drug-free remission by 36 months (10.5% vs. 2.7%, P = 0.006). The relative changes of anti-MDA5 antibody levels at the first three months (ΔMDA5@3m), with a cut-off point of 33.0% reduction, yielded a good predictive value for different seroconvertors with an area under curve of 0.86. Multivariable Cox regression model identified a reduction in ΔMDA5@3m of ≥ 33.0% as an independent favorable factor for achieving LDA (HR 1.96, 95% CI: 1.33–2.90, P < 0.001). Two distinct trajectories of anti-MDA5 antibody levels among 6-month survivors with anti-MDA5 + DM-ILD have been identified. The long-term outcomes were favorable for those with fast seroconvertors.