Background Progression of interstitial lung disease (ILD) is a candidate for long-term mortality in patients with systemic sclerosis (SSc). Different definitions of progression have been proposed. Declining lung function is often used, whereas others include composite definitions such as the 2022 ATS/ERS/JRS/ALAT guideline criteria for progressive pulmonary fibrosis (PPF) and the INBUILD criteria for progressive fibrosing ILD (PF-ILD). These different definitions have not been compared in SSc-ILD.

Objectives To estimate the prevalence of ILD progression applying different definitions and test their performance of predicting mortality.

Methods We included all SSc patients from the Oslo and Zurich cohorts who had ILD on HRCT and serial assessments of disease progression defined as:

• (A) Absolute FVC decline >5% over 12 months

• (B) PPF guideline criteria with 2/3 criteria present over 12 months of (1) worsening of respiratory symptoms; (2) absolute decline in FVC >5% or in DLCO >10% and (3) disease progression on HRCT

• (C) INBUILD PF-ILD criteria within 24 months with (1) FVC decline ≥10%, (2) FVC decline >5-<10% and worsening of respiratory symptoms or increased lung fibrosis on HRCT, or (3) worsening of respiratory symptoms and increased lung fibrosis.

We assessed the prevalence of ILD progression using these competing definitions and applied multivariable cox regression models (with hazards ratios (HR) and 95%CI) adjusted for known risk factors for mortality and compared the performance using Harrels c-index.

Results In total, 231 SSc-ILD patients from Oslo and Zurich were included, with 71 (31%) showing FVC decline >5%, 43 (19%) fulfilling the PPF guideline and 89 (39%) the INBUILD PF-ILD criteria. Most progressive patients fulfilled ≥1 definition of progression [60/107 (56%)] while 124 (54%) did not progress (Figure 1). Patient characteristics did not differ between the definitions, except for more extensive ILD and ground glass on HRCT and more frequent oxygen desaturation among those fulfilling the PPF criteria (Table 1). The number of deaths [44 (47%)] over mean 7.7 years (SD 3.9) follow up were comparable in the different groups. The progression definitions performed differently in multivariable cox models adjusted for age, sex, disease duration, SSc subtype, extent of lung fibrosis, baseline FVC and treatment using FVC decline>5% (HR1.87, 1.10-3.17 95%CI; p=0.020; c-index 0.7331), PPF guideline (HR1.42, 0.79-1.84 95%CI; p=0.231; c-index=0.7156) and INBUILD PF-ILD (HR 2.38, 1.40-4.04 95%CI: p<0.001; c-index=0.7338). The models discriminating ability was not significantly different (p=0.138).

Conclusion The prevalence of ILD progression varies depending on which definition was applied. FVC decline alone and PF-ILD criteria predicted mortality significantly but not the 2022 PPF guideline criteria.

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Acknowledgements: NIL.

Disclosure of Interests Anna-Maria Hoffmann-Vold Speakers bureau: Boehringer Ingelheim, Jannsen, Medscape, Merck Sharp & Dohme and Roche, Consultant of: ARXX, Boehringer Ingelheim, Genentech, Jannsen, Medscape, Merck Sharp & Dohme and Roche, Grant/research support from: Boehringer Ingelheim, Jannsen, Liubov Petelytska: None declared, Håvard Fretheim Speakers bureau: Boehringer Ingelheim, Grant/research support from: Jannsen, Imon Barua: None declared, Mike O. Becker Speakers bureau: Mepha, Bayer, MSD, GSK, Amgen, Novartis and Vifor outside the submitted work., Hilde Jenssen Bjørkekjær Grant/research support from: Jannsen, Cathrine Brunborg: None declared, Cosimo Bruni Speakers bureau: Eli-Lilly, Consultant of: Boehringer Ingelheim, Grant/research support from: Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC). Educational grants from AbbVie, Phuong Phuong Diep Speakers bureau: Boehringer-Ingelheim, Consultant of: Boehringer-Ingelheim, Rucsandra Dobrota Speakers bureau: Actelion and Boehringer-Ingelheim, congress support, Grant/research support from: Articulum Fellowship, sponsored by Pfizer (2013-2014), Actelion, Amgen, outside the submitted work, Michael Durheim Speakers bureau: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim, Muriel Elhai Consultant of: BMS, Grant/research support from: Support for travel (Janssen), Suzana Jordan: None declared, Emily Langballe: None declared, Øyvind Midtvedt: None declared, Carina Mihai Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Janssen, MED Talks Switzerland, Mepha, and PlayToKnow AG, Grant/research support from: Boehringer Ingelheim, Øyvind Molberg: None declared, Oliver Distler Speakers bureau: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur., Consultant of: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur.