. 2025 Oct 1;64(10):5344-5353.

doi: 10.1093/rheumatology/keaf264.

Lung function and skin fibrosis changes as predictors of survival in SSc-associated interstitial lung disease: a EUSTAR study

Vincent Sobanski^{1

2}, Jeska de Vries-Bouwstra³, Anna-Maria Hoffmann-Vold^{4

5}, Dörte Huscher⁶, Margarida Alves⁷, Marco Matucci-Cerinic^{8

9}, Gabriela Riemekasten¹⁰, Mengtao Li^{11

12}, László Czirják¹³, Otylia Kowal-Bielecka¹⁴, Yannick Allanore¹⁵, Nils Schoof¹⁶, Oliver Distler⁵; EUSTAR Collaborators

Collaborators, Affiliations

Collaborators

EUSTAR Collaborators:
Silvia Bellando Randone, Ulrich Walker, Florenzo Iannone, Britta Maurer, Radim Becvar, Antonella Riccardi, Elise Siegert, Simona Rednic, Jérome Avouac, Carlomaurizio Montecucco, Patricia E Carreira, Cecilia Varju, Carlo Chizzolini, Andrea Doria, Bernard Coleiro, Armando Gabrielli, Dominique Farge Bancel, Paolo Airò, Alexandra Balbir-Gurman, Alessandro Giollo, Christopher Denton, Nemanja Damjanov, Jörg Henes, Vera Ortiz Santamaria, Stefan Heitmann, Bojana Stamenkovic, Carlo Francesco Selmi, Mohammed Tikly, Lidia P Ananieva, Ariane Herrick, Ulf Müller-Ladner, Merete Engelhart, Eric Hachulla, Valeria Riccieri, Ruxandra Maria Ionescu, Ana Maria Gheorghiu, Jörg Distler, Francesca Ingegnoli, Vanessa Smith, Francesco Paolo Cantatore, Susanne Ullman, Piotr Wiland, Marie Vanthuyne, Juan Jose Alegre-Sancho, Kristine Herrmann, Ellen De Langhe, Branimir Anic, Maria Üprus, Sule Yavuz, Carolina de, Souza Müller, Svetlana Agachi, D'Alessandro Mathieu, Kamal Solanki, Douglas Veale, Esthela Loyo, Edoardo Rosato, Edoardo Rosato, Cristina-Mihaela Tanaseanu, Rosario Foti, Codrina Ancuta, Peter Villiger, Jacob van Laar, Nihal Fathi, Paloma García de la Peña Lefebvre, Jean Sibilia, Ira Litinsky, Francesco Del Galdo, Lesley Ann Saketkoo, Eduardo Kerzberg, Washington Bianchi, Ivan Castellví, Doron Rimar, Maura Couto, François Spertini, Sarah Kahl, Vivien M Hsu, Thierry Martin, Lorinda S Chung, Tim Schmeiser, Dominik Majewski, Vera Bernardino, Konstantinos Fourlakis, Elena Rezus

Affiliations

¹ Service de Médecine Interne, U1286 - INFINITE-Institute for Translational Research in Inflammation CHU Lille, Univ. Lille, Inserm, Lille, France.
² Institut Universitaire de France (IUF), Paris, France.
³ Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Rheumatology, Oslo University Hospital, Oslo, Norway.
⁵ Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁶ Institute of Biometry and Clinical Epidemiology, and Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁷ TA Inflammation Med, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.
⁸ Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), and Inflammation, Fibrosis and Aging Initiative (INFLAGE), IRCCS San Raffaele Scientific Institute, Rome, Italy.
⁹ Vita-Salute San Raffaele University, Milan, Italy.
¹⁰ Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
¹¹ Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
¹² Ministry of Education, Key Laboratory of Rheumatology and Clinical Immunology, Beijing, China.
¹³ Department of Rheumatology and Immunology, Medical School, University of Pecs, Pecs, Hungary.
¹⁴ Department of Rheumatology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
¹⁵ Rheumatology Department, Cochin Hospital APHP, INSERM U1016, Université Paris Cité, Paris, France.
¹⁶ Integrated Evidence Generation TA WHC, Bayer AG, Berlin, Germany.

PMID: 40457805
PMCID: PMC12494203
DOI: 10.1093/rheumatology/keaf264

Lung function and skin fibrosis changes as predictors of survival in SSc-associated interstitial lung disease: a EUSTAR study

Vincent Sobanski et al. Rheumatology (Oxford). 2025.

. 2025 Oct 1;64(10):5344-5353.

doi: 10.1093/rheumatology/keaf264.

Authors

Collaborators

EUSTAR Collaborators:
Silvia Bellando Randone, Ulrich Walker, Florenzo Iannone, Britta Maurer, Radim Becvar, Antonella Riccardi, Elise Siegert, Simona Rednic, Jérome Avouac, Carlomaurizio Montecucco, Patricia E Carreira, Cecilia Varju, Carlo Chizzolini, Andrea Doria, Bernard Coleiro, Armando Gabrielli, Dominique Farge Bancel, Paolo Airò, Alexandra Balbir-Gurman, Alessandro Giollo, Christopher Denton, Nemanja Damjanov, Jörg Henes, Vera Ortiz Santamaria, Stefan Heitmann, Bojana Stamenkovic, Carlo Francesco Selmi, Mohammed Tikly, Lidia P Ananieva, Ariane Herrick, Ulf Müller-Ladner, Merete Engelhart, Eric Hachulla, Valeria Riccieri, Ruxandra Maria Ionescu, Ana Maria Gheorghiu, Jörg Distler, Francesca Ingegnoli, Vanessa Smith, Francesco Paolo Cantatore, Susanne Ullman, Piotr Wiland, Marie Vanthuyne, Juan Jose Alegre-Sancho, Kristine Herrmann, Ellen De Langhe, Branimir Anic, Maria Üprus, Sule Yavuz, Carolina de, Souza Müller, Svetlana Agachi, D'Alessandro Mathieu, Kamal Solanki, Douglas Veale, Esthela Loyo, Edoardo Rosato, Edoardo Rosato, Cristina-Mihaela Tanaseanu, Rosario Foti, Codrina Ancuta, Peter Villiger, Jacob van Laar, Nihal Fathi, Paloma García de la Peña Lefebvre, Jean Sibilia, Ira Litinsky, Francesco Del Galdo, Lesley Ann Saketkoo, Eduardo Kerzberg, Washington Bianchi, Ivan Castellví, Doron Rimar, Maura Couto, François Spertini, Sarah Kahl, Vivien M Hsu, Thierry Martin, Lorinda S Chung, Tim Schmeiser, Dominik Majewski, Vera Bernardino, Konstantinos Fourlakis, Elena Rezus

Affiliations

¹ Service de Médecine Interne, U1286 - INFINITE-Institute for Translational Research in Inflammation CHU Lille, Univ. Lille, Inserm, Lille, France.
² Institut Universitaire de France (IUF), Paris, France.
³ Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Rheumatology, Oslo University Hospital, Oslo, Norway.
⁵ Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁶ Institute of Biometry and Clinical Epidemiology, and Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁷ TA Inflammation Med, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.
⁸ Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), and Inflammation, Fibrosis and Aging Initiative (INFLAGE), IRCCS San Raffaele Scientific Institute, Rome, Italy.
⁹ Vita-Salute San Raffaele University, Milan, Italy.
¹⁰ Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
¹¹ Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
¹² Ministry of Education, Key Laboratory of Rheumatology and Clinical Immunology, Beijing, China.
¹³ Department of Rheumatology and Immunology, Medical School, University of Pecs, Pecs, Hungary.
¹⁴ Department of Rheumatology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
¹⁵ Rheumatology Department, Cochin Hospital APHP, INSERM U1016, Université Paris Cité, Paris, France.
¹⁶ Integrated Evidence Generation TA WHC, Bayer AG, Berlin, Germany.

PMID: 40457805
PMCID: PMC12494203
DOI: 10.1093/rheumatology/keaf264

Abstract

Objectives: This study assessed how changes in lung function, skin fibrosis and digital ulceration (DU) burden predict mortality in patients with SSc-associated interstitial lung disease (SSc-ILD), the leading cause of death in SSc.

Methods: Adult SSc-ILD patients from the European Scleroderma Trials and Research (EUSTAR) database enrolled since January 2009 with a date of diagnosis, a follow-up visit for change evaluation within 12 months plus a further visit or mortality information were eligible. Twelve-month changes in lung function (per cent predicted forced vital capacity [FVC%pred] and diffusing capacity of the lungs for carbon monoxide [DLCO%pred]), modified Rodnan skin score (mRSS) and change in DU burden were assessed for associations with survival, using multivariable Cox regression analyses adjusted for age, sex, smoking status and immunosuppressive therapy.

Results: Of 893 SSc-ILD patients included, 94 (10.5%) died over a mean follow-up of 39.0 ± 23.9 months. Absolute deterioration in FVC >10%pred within 12 months (n = 78/638 evaluable) was predictive for decreased survival (hazard ratio [HR] 3.81; 95% CI 1.67-8.66), as were composite measures combining (i) >10% FVC decline or mRSS worsening (HR 2.82; 95% CI 1.43-5.56) and (ii) FVC decline ≥10% or 5-9% with DLCO decline ≥15% (HR 3.42; 95% CI 1.68-7.00), but not changes in DLCO, mRSS or DU burden alone.

Conclusions: Changes in lung function and skin fibrosis within 12 months should be considered when evaluating risk of mortality. The effect of pharmacological treatments aiming at stabilization of these variables should be evaluated prospectively in clinical trials.

Keywords: SSc-ILD; interstitial lung disease; mortality; prognostic stratification; systemic sclerosis.

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Figures

**Figure 1.**
Flow chart of the patients through the study. EUSTAR, European Scleroderma Trials and Research; HRCT, high-resolution CT; ILD, interstitial lung disease; SSc-ILD, SSc-associated interstitial lung disease

**Figure 2.**
Overall survival according to (A) change in FVC, (B) change in FVC and/or DL_CO and (C) change in FVC and/or mRSS. All changes within 12 months of the baseline visit. Categories for FVC and DL_CO are based on %pred values. %pred, per cent predicted; DL_CO, diffusing capacity of the lungs for carbon monoxide; FVC, forced vital capacity; mRSS, modified Rodnan skin score

See this image and copyright information in PMC

References

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Lung function and skin fibrosis changes as predictors of survival in SSc-associated interstitial lung disease: a EUSTAR study

Collaborators

Affiliations

Lung function and skin fibrosis changes as predictors of survival in SSc-associated interstitial lung disease: a EUSTAR study

Authors

Collaborators

Affiliations

Abstract

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical