Serum Type I Interferon Score for Prediction of Clinically Meaningful Disease Progression in Limited Cutaneous Systemic Sclerosis.

Di Donato, S.; Ross, R.; Karanth, R.; Kakkar, V.; De Lorenzis, E.; Bissell, LA.; Clark, K.; Yee, P.; Denton, CP.; Del Galdo, F.

Serum Type I Interferon Score for Prediction of Clinically Meaningful Disease Progression in Limited Cutaneous Systemic Sclerosis.

All Authors

Di Donato, S.

Ross, R.

Karanth, R.

Kakkar, V.

De Lorenzis, E.

Bissell, LA.

Clark, K.

Yee, P.

Denton, CP.

Del Galdo, F.

LTHT Author

Di Donato, Stefano
Kakkar, Vishal
Bissell, Leslie-Anne
Del Galdo, Francesco

LTHT Department

NIHR Leeds Biomedical Research Centre
Rheumatology

Publication Date

2025

Item Type

Journal Article
Observational Study
Multicenter Study

Abstract

OBJECTIVE: To assess the value of serum type I interferon (IFN) score in predicting clinically meaningful progression in limited cutaneous systemic sclerosis (lcSSc) using a novel composite endpoint adopted from the MINIMISE clinical trial. METHODS: A retrospective, longitudinal lcSSc cohort was identified within a national, multicenter observational cohort. The MINIMISE trial combined Morbi-mortality endpoint was used as the clinical outcome for a time to clinical worsening (TTCW) design. The IFN score was calculated from the serum concentration of chemokine C-C motif ligand (CCL) 2, CCL8, CCL19, C-X-C motif chemokine ligand (CXCL) 9, CXCL10, and CXCL11 on patients and age- and sex-matched healthy controls (HCs). A "high" IFN score was defined as 2 SDs above the HC mean. The association of the IFN score with TTCW was assessed using Cox proportional hazard regressions and Kaplan-Meier curves. The potential improvement in risk stratification when combining IFN score with lcSSc clinical features was explored. RESULTS: A total of 149 patients were included in the analysis: 67 "high" IFN and 82 "low." High IFN patients presented a shorter TTCW (74.7 months [95% confidence interval (CI) 70.1-79.3] vs 110.6 months [95% CI 107.2-114.0]; P < 0.001) and met the endpoint in higher proportion compared with low IFN (55% vs 12%; P < 0.001). A high IFN score conferred hazard ratio (HR) 5.5 (95% CI 2.7-11.3) for TTCW compared with low IFN, and IFN score as a continuous variable conferred HR 2.38 (95% CI 1.4-4.0) for TTCW independently of clinical variables. Pulmonary arterial hypertension, interstitial lung disease, digital ulcers, and modified Rodnan skin score were associated with TTCW. An exploratory analysis showed that these clinical features improve risk stratification over time in combination with IFN score. CONCLUSION: Serum assessment of type I IFN activity is a valuable predictor of clinically meaningful outcomes in lcSSc. The combination of serum IFN score with sentinel clinical features can improve stratification strategies in clinical trials and patient management.