Occurrence of progressive pulmonary fibrosis and its association with survival in connective tissue disease-associated interstitial lung disease: an international retrospective cohort study.

To describe real-world management of connective tissue disease-associated interstitial lung disease (CTD-ILD) and explore associations between progressive pulmonary fibrosis (PPF) onset and clinical outcomes. This international, retrospective cohort included adults with rheumatoid arthritis (RA), systemic sclerosis (SSc), mixed connective tissue disease, and other CTD with associated ILD. PPF was identified using INBUILD and/or ATS/ERS/JRS/ALAT criteria applied in routine care. Analyses were descriptive and exploratory; time-to-event methods assessed selected outcomes and factors associated with PPF onset. Among 357 patients (mean age 61.6 years; 58% female), SSc-ILD (31%) and RA-ILD (29%) were most common. At ILD diagnosis, 21.6% had no respiratory symptoms. During a mean follow-up of 60.5 months, 147 patients (41.2%) met the PPF criteria, at a median of 30.6 months after CTD-ILD diagnosis. Following PPF onset, the most frequently prescribed therapies were corticosteroids (72.8%), mycophenolate mofetil (52.4%), and antifibrotics (51.0%). Lung function data were available for 37.8% at diagnosis and 53.7% at year 5. PPF was associated with greater observed lung function decline compared to non-PPF patients. ILD-related hospitalizations was numerically more frequent within PPF patients (37.4% vs. 28.6%), but the difference was not statistically significant (P = 0.078). Among patients with PPF, earlier versus later onset, defined by a subtype-specific median split, was associated with poorer observed survival (P < 0.001). In this retrospective cohort, PPF was observed frequently in CTD-ILD patients, particularly those with SSc-ILD, and was associated with greater lung function decline and higher healthcare utilisation. Earlier PPF onset was associated with higher mortality risk, but missing lung function data, surveillance differences, time-related bias, and residual confounding limit causal interpretation. Prospective studies using harmonised PPF adjudication and time-dependent analyses are needed.