Survival and immunomodulatory therapy in autoimmune disease-associated progressive pulmonary fibrosis: a multicenter registry (NEREA)

OBJECTIVES: To assess the mortality rate related to interstitial lung disease (ILD) in autoimmune-ILD patients with progressive pulmonary fibrosis (PPF), and to evaluate the role of immunomodulatory therapy and other variables in the ILD-related mortality. METHODS: A longitudinal multicenter study was conducted in autoimmune ILD from 2005 to 2024 in Madrid. Patients were those enrolled in NEREA [pNEumology RhEumatology Autoinmune] registry who met PPF criteria. Main outcome was specific-cause mortality related to ILD. Independent variable: immunomodulatory therapy. Covariates: sociodemographic, clinical, other treatments. Survival techniques were used to estimate the cause specific mortality rate due to ILD (MR) and 95%CI, expressed per 100 patients-year. Fine-Gray competing risk regression models assessed the risk of immunomodulatory therapy on ILD-related mortality (results expressed as subhazard ratio (SHR) and 95%CI). RESULTS: Among 158 patients, 70.3% were on immunomodulatory therapy at PPF baseline, increasing to 81% during follow-up. 47 deaths were documented, and 79% of them were attributed to ILD-related causes with a MR of 6.2 [4.5-8.5]. MR was lower in patients who received immunomodulatory therapy, with a mean survival of 4.8 years in untreated patients and over 10 years in those who received treatment. Immunomodulatory therapy improved survival regardless other factors (SHR: 0.35 [0.19-0.66], p = 0.001). Additionally, a worse diffusing capacity for carbon monoxide (DLCO)% (<60), and to have emphysema independently increased the risk of ILD-related mortality. CONCLUSION: The study shows a considerable mortality directly attributable to ILD. Furthermore, it demonstrates a survival benefit in patients receiving immunomodulatory therapy regardless other factors.