Abstract
OBJECTIVES: To assess factors associated with rapidly progressive interstitial lung disease (ILD) (RP-ILD) at time of ILD diagnosis in a multicentric retrospective cohort study of antisynthetase syndrome (ASyS). We used a complementary unsupervised approach, hierarchical clustering, to delineate distinct phenotypes among ASyS patients with ILD. METHODS: A total of 132 patients with ASyS, defined according to the 2024 ACR/European Alliance of Associations for Rheumatology (EULAR) ASyS classification criteria, and ILD, diagnosed by CT scan, were included. RP-ILD was defined by the presence of respiratory failure at ILD diagnosis or rapid ILD progression during the first 3 months. RESULTS: In our study, 39% of patients had RP-ILD at ILD diagnosis. Multivariate logistic regression analysis with cluster-robust SE identified the factors associated with RP-ILD at ILD diagnosis as male sex (aOR = 9.7 [1.6-59.5], p = 0.006), fever (aOR = 128 [12.6-1300], p < 0.001), organizing pneumonia (OP) pattern (aOR = 66.8 [3.4-1316], p = 0.006), and pleural effusion (aOR = 20.2 [1.1-373], p = 0.04), whereas RP-ILD was associated with lower likelihood of severe muscle disease (aOR = 0.004 [0.0001-0.13], p = 0.002). Clustering analysis identified four distinct groups: Cluster 1 (n = 62) included patients with systemic presentation, non-RP-ILD at ILD diagnosis, and anti-Jo-1 antibodies with good prognosis; Cluster 2 (n = 40) included older age patients with more RP-ILD at ILD diagnosis, pleuropericarditis, and a higher mortality rate. CONCLUSION: Fever, pleural effusion, and OP pattern were independently associated with RP-ILD in ASyS patients. Unsupervised cluster analysis identified a severe inflammatory phenotype in ASyS patients with ILD.