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. 2021 Feb;80(2):219-227.
doi: 10.1136/annrheumdis-2020-217455. Epub 2020 Sep 28.

Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database

Anna-Maria Hoffmann-Vold  1 , Yannick Allanore  2 , Margarida Alves  3 , Cathrine Brunborg  4 , Paolo Airó  5 , Lidia P Ananieva  6 , László Czirják  7 , Serena Guiducci  8 , Eric Hachulla  9 , Mengtao Li  10 , Carina Mihai  11 , Gabriela Riemekasten  12 , Petros P Sfikakis  13 , Otylia Kowal-Bielecka  14 , Antonella Riccardi  15 , Oliver Distler  16 ; EUSTAR collaborators
Collaborators, Affiliations

Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database

Anna-Maria Hoffmann-Vold et al. Ann Rheum Dis. 2021 Feb.

Abstract

Objectives: To identify overall disease course, progression patterns and risk factors predictive for progressive interstitial lung disease (ILD) in patients with systemic sclerosis-associated ILD (SSc-ILD), using data from the European Scleroderma Trials And Research (EUSTAR) database over long-term follow-up.

Methods: Eligible patients with SSc-ILD were registered in the EUSTAR database and had measurements of forced vital capacity (FVC) at baseline and after 12±3 months. Long-term progressive ILD and progression patterns were assessed in patients with multiple FVC measurements. Potential predictors of ILD progression were analysed using multivariable mixed-effect models.

Results: 826 patients with SSc-ILD were included. Over 12±3 months, 219 (27%) showed progressive ILD: either moderate (FVC decline 5% to 10%) or significant (FVC decline >10%). A total of 535 (65%) patients had multiple FVC measurements available over mean 5-year follow-up. In each 12-month period, 23% to 27% of SSc-ILD patients showed progressive ILD, but only a minority of patients showed progression in consecutive periods. Most patients with progressive ILD (58%) had a pattern of slow lung function decline, with more periods of stability/improvement than decline, whereas only 8% showed rapid, continuously declining FVC; 178 (33%) experienced no episode of FVC decline. The strongest predictive factors for FVC decline over 5 years were male sex, higher modified Rodnan skin score and reflux/dysphagia symptoms.

Conclusion: SSc-ILD shows a heterogeneous and variable disease course, and thus monitoring all patients closely is important. Novel treatment concepts, with treatment initiation before FVC decline occurs, should aim for prevention of progression to avoid irreversible organ damage.

Keywords: autoimmune diseases; pulmonary fibrosis; scleroderma; systemic.

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Conflict of interest statement

Competing interests: A-MH-V received research funding and/or consulting fees or other remuneration from Actelion, Boehringer Ingelheim, Roche, Bayer, Thermo Fisher, MSD, Arxx and Medscape. YA received research funding and/or consulting fees from Actelion, Alpine, Bayer, BMS, Boehringer Ingelheim, Inventiva, Italfarmaco, Genentech Roche, Sanofi and Servier. MA is an employee of Boehringer Ingelheim. LA received consulting fees or other remuneration from Boehringer Ingelheim and Roche. LC received consulting fees from Actelion, Bayer, Boehringer Ingelheim, Medac, Pfizer and Roche. EH received research funding and/or consulting fees or other remuneration from Actelion, Bayer, GSK and Pfizer. CM received consulting fees or other remuneration from Actelion, Geneva, Roche and Rofarm. OK-B received consulting fees or other remuneration from Bayer, Boehringer Ingelheim, Inventiva, Medac, Novartis and Roche. OD received consulting fees and/or research funding from A.Menarini, Acceleron Pharma, Amgen, AnaMar, Bayer, Blade Therapeutics, Boehringer Ingelheim, Catenion, CSL Behring, ChemomAb, Ergonex, Glenmark Pharmaceuticals, GSK, Inventiva, Italfarmaco, iQone, IQVIA, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Target Bioscience and UCB in the area of potential treatments of scleroderma and its complications, and holds Patent mir 29 for the treatment of systemic sclerosis (US8247389, EP2331143). CB, PA, SG, ML, GR, AR and PPS have no competing interests to disclose.

Figures

Figure 1
Figure 1
FVC changes among patients with SSc-ILD in the EUSTAR database (number of patients per category): (A) overall change during the 5-year follow-up period; (B) changes during each 12-month follow-up period. (A) Patients for whom ≥3 serial FVC measurements were available were divided into five disease course subgroups based on the overall difference between the first and last FVC measurement (% predicted): major decline (FVC decline of >20%); significant decline (FVC decline of >10% to 20%); moderate decline (FVC decline of 5% to 10%); stable (FVC decline or improvement of <5%); and improvement (FVC improvement of ≥5%). (B) Disease course each year was evaluated by determining the magnitude of FVC changes (% predicted) in each 12-month period during the mean 5-year follow-up defined as follows: significant decline (FVC decline of >10%); moderate decline (FVC decline of 5% to 10%); stable (FVC decline or improvement of <5%); and improvement (FVC improvement of ≥5%). EUSTAR, European Scleroderma Trials And Research; FVC, forced vital capacity; SSc-ILD, systemic sclerosis-associated interstitial lung disease.
Figure 2
Figure 2
FVC changes in consecutive 12-month periods among patients with SSc-ILD in the EUSTAR database (number of patients per category): (A) subsequent course among patients with stable or improved FVC during the first year of follow-up; (B) subsequent course among patients with minor or moderate decline during the first year of follow-up and those who had further declines. Disease course each year was evaluated by determining the magnitude of FVC changes (% predicted) in individual patients in each 12-month period during the mean 5-year follow-up, defined as follows: significant decline (FVC decline of >10%); moderate decline (FVC decline of 5% to 10%); stable (FVC decline or improvement of <5%); and improvement (FVC improvement of ≥5%). EUSTAR, European Scleroderma Trials And Research; FVC, forced vital capacity; SSc-ILD, systemic sclerosis-associated interstitial lung disease.
Figure 3
Figure 3
Patterns of disease course in SSc-ILD. Overall disease course was evaluated by determining the magnitude of FVC changes (% predicted) in individual patients from baseline to the end of follow-up defined as follows: major decline (FVC decline of >20%); significant decline (FVC decline of 10% to 20%); moderate decline (FVC decline of 5% to 10%); stable (FVC decline or improvement of <5%); and improvement (FVC improvement of ≥5%). Patterns of disease progression are shown in patients with improved FVC, stable FVC and those with significant or major decline. FVC, forced vital capacity; SSc-ILD, systemic sclerosis-associated interstitial lung disease.
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