P138 Serum type I interferon activity as a biomarker of morbimortality in systemic sclerosis independent of cutaneous subset

Abstract Background/Aims Systemic sclerosis (SSc) is a heterogeneous autoimmune disease traditionally stratified by cutaneous subset, with diffuse (dcSSc) linked to severe organ involvement and higher mortality, and limited (lcSSc) associated with prevalent vascular morbidity. However, skin phenotype alone may not fully capture disease heterogeneity. Elevated IFN scores correlate with adverse outcomes, yet it remains unclear whether this effect is independent of cutaneous subset. This study evaluates the prognostic role of serum type I IFN activity across lcSSc and dcSSc, testing its independent contribution. Methods The interferon (IFN) score was calculated, as previously described (Ross et al.), from serum concentrations of CCL2, CCL8, CCL19, CXCL9, CXCL10, and CXCL11 (Myriad RBM) in patients with systemic sclerosis (SSc) fulfilling the 2013 ACR/EULAR classification criteria, who were retrospectively selected from the STRIKE national, multicentre observational cohort. The combined morbi-mortality endpoint from the MINIMISE trial was used as clinical outcome, with time-to-event analyses starting from the date of serum sampling. Baseline characteristics were compared using standard parametric and non-parametric tests, and survival analyses. Results A total of 221 SSc patients were included in the analysis (Table 1). Patients with a high IFN score showed significantly reduced event-free survival compared with those with low IFN (Log-rank X²=22, p 0.001); similarly, dcSSc patients had worse survival than lcSSc (Log-rank X²=17, p 0.001), as shown by Kaplan-Meier time-to-event analysis. A high IFN score conferred a 2.57-fold increased risk of adverse outcomes (95% CI 1.64-4.03, p 0.001, multivariable Cox proportional hazard models) after adjustment for established prognostic factors, including cutaneous subset. The IFN score maintained a hazard ratio of 1.60 (95% CI 1.18-2.16, p = 0.002), even when analysed as a continuous variable, suggesting that IFN activation is a robust predictor of adverse outcomes across different disease subsets. The interaction analysis confirmed the independence of IFN, since no significant effect modification was detected between IFN score and cutaneous subset (p = 0.42). Conclusion Serum Type I IFN activity demonstrates clear prognostic value in SSc, being strongly associated with morbi-mortaliy outcomes regardless of cutaneous subset. This independence from disease phenotype highlights the IFN score as a robust biomarker for risk stratification in both clinical care and trial design. Disclosure V. Batani: None. S. Di Donato: None. R. Ross: None. M. Minerba: None. E. De Lorenzis: None. V. Kakkar: None. C. Denton: None. F. Del Galdo: None.