Di Donato, Stefano;
Ross, Rebecca;
Karanth, Ranjitha;
Kakkar, Vishal;
De Lorenzis, Enrico;
Bissell, Lesley-Anne;
Clark, Kristina;
... Del Galdo, Francesco; + view all
(2025)
Serum Type I Interferon Score for Prediction of Clinically Meaningful Disease Progression in Limited Cutaneous Systemic Sclerosis.
Arthritis & Rheumatology
10.1002/art.43120.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Serum Type I Interferon Score for Prediction of Clinically Meaningful Disease Progression in Limited Cutaneous Systemic Sclerosis |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/art.43120 |
| Publisher version: | https://doi.org/10.1002/art.43120 |
| Language: | English |
| Additional information: | © 2025 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10206146 |
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