Background/Purpose: Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5+DM) is a distinct and severe subtype of dermatomyositis, frequently complicated by interstitial lung disease (ILD). Among these patients, rapid progressive ILD (RP-ILD) is the leading cause of high mortality, often resulting in severe respiratory failure within a short time frame. Despite available treatments, managing MDA5+ DM-associated ILD (MDA5+DM-ILD) remains a significant clinical challenge, with first-year mortality rates reported as high as 40%. Therefore, exploring effective therapeutic options is crucial. This cohort study aims to evaluate the efficacy and safety of Upadacitinib (UPA) in patients with MDA5+ DM-ILD, assessing its potential to improve clinical outcomes.

Methods: All patients with MDA5+DM-ILD who were admitted to Renji Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, between 2013 and 2024 were included in the study. The primary efficacy endpoint was the 1-year survival rate. Secondary efficacy endpoints included the dosage of glucocorticoid usage, changes in lung function, and relevant laboratory parameters. Propensity score matching (PSM) was applied to minimize confounding biases and enhance intergroup comparability.

Results: In the eligible cohort, a total of 49 patients received UPA treatment, while 377 patients were in the non-UPA group, of whom 78.5% received tofacitinib. After propensity score matching (PSM), baseline differences between the two groups were reduced (Table 1). The 1-year survival rates were 79.6% (39/49) in the UPA group and 60.5% (228/377) in the non-UPA group. Following PSM, the 1-year survival rate of the non-UPA group was 58.5%, with the difference remaining statistically significant (P=0.031) (Figure 1). Multivariate Cox regression analysis after PSM indicated that UPA treatment was associated with a significantly lower mortality risk, with a hazard ratio (HR) of 0.491 (95% confidence interval: 0.251-0.960) compared to the non-UPA group (Figure 2A). Subgroup analyses further demonstrated that UPA provided greater therapeutic benefits in patients with PaO₂/FiO₂ ratios between 200-300 mmHg (Figure 2B).

Conclusion: In this cohort study, UPA demonstrated a superior ability to improve the survival of patients with MDA5+DM-ILD compared to the non-UPA treatment regimen.

Table 1 Demographic data in the UPA group and the non-UPA group before and after PSM.

PSM, propensity score matching; UPA, Upadacitinib; SMD, standard mean difference; ILD, interstitial lung disease; RP-ILD, rapidly progressive interstitial lung disease; FVC, forced vital capacity.

*p＜0.05

Figure 1 Kaplan-Meier survival curves comparing UPA group and non-UPA group patients before and after PSM.

Figure 2 Prognostic analysis and subgroup treatment outcomes of UPA in MDA5+DM-ILD Patients. (A) Multivariate Cox regression forest plots for prognostic factors. (B) Subgroup analysis of treatment outcomes.

Predmax, maximum prednisone dose; SF, serum ferritin; NLR, neutrophil-to-lymphocyte ratio; LDH, lactate dehydrogenase; CRP, C-reactive protein; RP-ILD, rapidly progressive interstitial lung disease; FVC, forced vital capacity.

*P < 0.05.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-and-efficacy-of-upadacitinib-in-melanoma-differentiation-associated-gene-5-positive-dermatomyositis-with-interstitial-lung-disease-a-single-centre-retrospective-propensity-score-matched-coho/