Fibrotic Morphology and Survival in Interstitial Pneumonia with Autoimmune Features

Application of the 2015 Interstitial Pneumonia with Autoimmune Features (IPAF) research statement produced IPAF cohorts with favorable transplant-free survival (TFS) relative to the idiopathic interstitial pneumonia (IP) base populations from which they arose. Whether differences in underlying fibrotic morphology may explain this observation remains unclear.A multi-centre retrospective cohort study was performed. IPAF criteria were applied to six idiopathic IP cohorts from the US and UK using available clinical data. Fibrotic morphology was determined in separate analyses using imaging and histopathological data. Three-year TFS was compared between cohorts before and after adjustment for fibrotic morphology. Stratified analyses were performed to assess the prognostic significance of IPAF classification and presence clinical and serological domain features within key morphological groups. Outcomes were benchmarked against a connective tissue disease-associated (CTD-ILD) reference cohort (n=1566).Of 5042 individuals with idiopathic IP included in the analysis, 649 (12.9%) met IPAF criteria. Whilst IPAF classification was associated with favorable TFS before adjustment for imaging-based fibrotic morphology (HR 0.79; 95% CI 0.68-0.92; p=0.003), this association was attenuated after adjustment (HR 0.91; 95% CI 0.77-1.07; p=0.25). Results were similar when adjusting for histopathological-based morphology. IPAF classification had no prognostic significance within common morphological groups, but the presence of IPAF clinical domain features captured a phenotype with CTD-ILD-like natural history in the setting of non-UIP morphology.After accounting for differences in fibrotic morphology, IPAF classification has no prognostic significance relative to the idiopathic IP base population, suggesting that the current IPAF construct may not effectively identify a unique population.