The final forward model, including disease duration, VAS lung impairment, mRSS, and disease activity score, along with previously tested laboratory data, showed that ICAM1 + EVs (HR 1.1, 95% CI 1.02–1.1), and IL6 (HR 1.1, 95% CI 1.03–1.2) were independent predictors of SSc-ILD progression. This evidence concerns the gene ICAM1 and systemic sclerosis.