A Systematic Review of the Key Predictors of Progression and Mortality of Rheumatoid Arthritis-Associated Interstitial Lung Disease

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is an important extra-articular manifestation of rheumatoid arthritis (RA). Identifying patients at risk of progression and death is crucial for improving RA-ILD management and outcomes. This paper explores current evidence on prognostic factors in RA-ILD. Methods: We conducted a systematic literature review to examine the impact of clinical, radiological, and histological factors on lung function decline and the survival of RA-ILD patients. We searched electronic databases, including Medline and EMBASE, from inception to date. The incidence and prognosis of predictors were qualitatively analyzed, and univariate results were combined when feasible. Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines, our systematic literature review involved a five-step algorithm. Out of 2217 records, 48 studies were eligible. These studies reported various prognostic factors, including demographic variables, clinical risk factors, serum markers, and preexisting treatments. Results: Lung function declined over time in 1225 subjects, with significant variability in smoking history and radiological/pathological UIP patterns. Severe lung fibrosis and abnormal pulmonary function tests (PFTs) were key univariate prognostic indicators, while age at initial presentation, RA disease activity, predicted DLCO percentage, and UIP pattern were the most reliable multivariate risk factors for ILD progression. Age, male gender, disease duration, RA activity, acute phase reactants, and specific serum biomarkers (Krebs vin den Lungen 6, surfactant protein D, and interleukin 6) were significantly associated with all-cause mortality. Conclusions: RA-ILD is a severe complication of RA characterized by significant prognostic variability. Key prognostic factors include extensive fibrosis observed on imaging, a marked decline in lung function, high RA disease activity, and specific biomarkers. These factors can guide treatment strategies and improve patient outcomes.